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Review Article

Human cytochrome P450 enzymes 5–51 as targets of drugs and natural and environmental compounds: mechanisms, induction, and inhibition – toxic effects and benefits

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Pages 256-342 | Received 22 Mar 2018, Accepted 14 May 2018, Published online: 16 Dec 2018

References

  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Guengerich FP. 2017. Intersection of the roles of cytochrome P450 enzymes with xenobiotic and endogenous substrates: relevance to toxicity and drug interactions. Chem Res Toxicol. 30:2–12.
  • Guengerich FP, Cheng Q. 2011. Orphans in the human cytochrome P450 superfamily: approaches to discovering functions and relevance in pharmacology. Pharmacol Rev. 63:684–699.
  • Guengerich FP, Rendic S. 2010. Update information on drug metabolism systems–2009, part I. Curr Drug Metab. 11:1–3.
  • Klammert U, Nickel J, Wurzler K, Klingelhoffer C, Sebald W, Kubler AC, Reuther T. 2009. Biological activity of a genetically modified BMP-2 variant with inhibitory activity. Head Face Med. 5:6.
  • Rendic S, Guengerich FP. 2010. Update information on drug metabolism systems–2009, part II: summary of information on the effects of diseases and environmental factors on human cytochrome P450 (CYP) enzymes and transporters. Curr Drug Metab. 11:4–84.
  • Rendic S, Guengerich FP. 2012. Summary of information on the effects of ionizing and non-ionizing radiation on cytochrome P450 and other drug metabolizing enzymes and transporters. Curr Drug Metab. 13:787–814.
  • Rendic S, Guengerich FP. 2015. Survey of human oxidoreductases and cytochrome P450 enzymes involved in the metabolism of xenobiotic and natural chemicals. Chem Res Toxicol. 28:38–42.
  • Semonin-Holleran R. 1991. Pediatric trauma patients: differences and implications for emergency nurses. J Emergen Nurs. 17:24–33.

References

  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Li YC, Chiang CW, Yeh HC, Hsu PY, Whitby FG, Wang LH, Chan NL. 2008. Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligand-specific heme conformation change. J Biol Chem. 283:2917–2926.

References

  • Ackerley N, Brewster AG, Brown GR, Clarke DS, Foubister AJ, Griffin SJ, Hudson JA, Smithers MJ, Whittamore PR. 1995. A novel approach to dual-acting thromboxane receptor antagonist/synthase inhibitors based on the link of 1,3-dioxane-thromboxane receptor antagonists and -thromboxane synthase inhibitors. J Med Chem. 38:1608–1628.
  • Casey MB, Zhang S, Jin L, Kajita S, Lloyd RV. 2004. Expression of cyclooxygenase-2 and thromboxane synthase in non-neoplastic and neoplastic thyroid lesions. Endocr Pathol. 15:107–116.
  • Cathcart MC, Reynolds JV, O'Byrne KJ, Pidgeon GP. 2010. The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer. Biochim Biophys Acta. 1805:153–166.
  • Cimetiere B, Dubuffet T, Landras C, Descombes JJ, Simonet S, Verbeuren TJ, Lavielle G. 1998. New tetrahydronaphthalene derivatives as combined thromboxane receptor antagonists and thromboxane synthase inhibitors. Bioorg Med Chem Lett. 8:1381–1386.
  • Davi G, Santilli F, Vazzana N. 2012. Thromboxane receptors antagonists and/or synthase inhibitors. Handb Exp Pharmacol. (210):261–286.
  • de Leval X, Benoit V, Delarge J, Julemont F, Masereel B, Pirotte B, Merville MP, David JL, Dogne JM. 2003. Pharmacological evaluation of the novel thromboxane modulator BM-567 (II/II). Effects of BM-567 on osteogenic sarcoma-cell-induced platelet aggregation. Prostaglandins Leukot Essent Fatty Acids. 68:55–59.
  • de Leval X, Dassesse T, Dogne JM, Waltregny D, Bellahcene A, Benoit V, Pirotte B, Castronovo V. 2006. Evaluation of original dual thromboxane A2 modulators as antiangiogenic agents. J Pharmacol Exp Ther. 318:1057–1067.
  • Ding ZQ, Rowe J, Ng B, Sinosich MJ, Gallery ED. 2002. Modulation of prostacyclin and thromboxane secretion by cytotrophoblasts from normal and pre-eclamptic human pregnancies. Placenta. 23:594–599.
  • Dogne JM, de Leval X, Delarge J, David JL, Masereel B. 2000. New trends in thromboxane and prostacyclin modulators. Curr Med Chem. 7:609–628.
  • Dogne JM, de Leval X, Hanson J, Frederich M, Lambermont B, Ghuysen A, Casini A, Masereel B, Ruan KH, Pirotte B, et al. 2004. New developments on thromboxane and prostacyclin modulators, part I: thromboxane modulators. Curr Med Chem. 11:1223–1241.
  • Dogne JM, Hanson J, de Leval X, Pratico D, Pace-Asciak CR, Drion P, Pirotte B, Ruan KH. 2006. From the design to the clinical application of thromboxane modulators. Curr Pharmaceut Design. 12:903–923.
  • Dogne JM, Rolin S, de Leval X, Benoit P, Neven P, Delarge J, Kolh P, Damas J, David JL, Masereel B. 2001. Pharmacology of the thromboxane receptor antagonist and thromboxane synthase inhibitor BM-531. Cardiovasc Drug Rev. 19:87–96.
  • Dogne JM, Wouters J, Rolin S, Michaux C, Pochet L, Durant F, Delarge J, Masereel B. 2001. Design, synthesis and biological evaluation of a sulfonylcyanoguanidine as thromboxane A2 receptor antagonist and thromboxane synthase inhibitor. J Pharm Pharmacol. 53:669–680.
  • Faull AW, Brewster AG, Brown GR, Smithers MJ, Jackson R. 1995. Dual-acting thromboxane receptor antagonist/synthase inhibitors: synthesis and biological properties of [2-substituted-4-(3-pyridyl)-1,3-dioxan-5-yl] alkenoic acids. J Med Chem. 38:686–694.
  • Ford NF, Browne LJ, T, Gemenden, C, Goldstein, R, Gude C, Wasley JW. 1985. Imidazo[1,5-a]pyridines: a new class of thromboxane A2 synthetase inhibitors. J Med Chem. 28:164–170.
  • Ghuysen A, Dogne JM, Chiap P, Rolin S, Masereel B, Lambermont B, Kolh P, Tchana-Sato V, Hanson J, D'Orio V. 2005. Pharmacological profile and therapeutic potential of BM-573, a combined thromboxane receptor antagonist and synthase inhibitor. Cardiovasc Drug Rev. 23:1–14.
  • Goerig M, Habenicht AJ. 1988. Effects of nicotine on eicosanoid synthesis of differentiating human promyelocytic leukemia cells. Klin Wochenschrift. 66(Suppl 11):117–119.
  • Goerig M, Ullrich V, Schettler G, Foltis C, Habenicht A. 1992. A new role for nicotine: selective inhibition of thromboxane formation by direct interaction with thromboxane synthase in human promyelocytic leukaemia cells differentiating into macrophages. Clin Investigator. 70:239–243.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Hanson J, Rolin S, Reynaud D, Qiao N, Kelley LP, Reid HM, Valentin F, Tippins J, Kinsella BT, Masereel B, et al. 2005. In vitro and in vivo pharmacological characterization of BM-613 [N-n-pentyl-N´-[2-(4´-methylphenylamino)-5-nitrobenzenesulfonyl]urea], a novel dual thromboxane synthase inhibitor and thromboxane receptor antagonist. J Pharmacol Exp Ther. 313:293–301.
  • Hartmann RW, Frotscher M. 1999. 1-Imidazolylcarbonyloxy-substituted tetrahydroquinolines and pyridines: synthesis and evaluation of P450 TxA2 inhibition. Archiv Pharm. 332:358–362.
  • Hartmann RW, Frotscher M, Ledergerber D, Wachter GA, Grun GL, Sergejew TF. 1996. Synthesis and evaluation of azole-substituted tetrahydronaphthalenes as inhibitors of P450arom, P450 17, and P450 TxA2. Archiv Pharm. 329:251–261.
  • Hecker M, Ullrich V. 1989. On the mechanism of prostacyclin and thromboxane A2 biosynthesis. J Biol Chem. 264:141–150.
  • Heinisch G, Holzer W, Kunz F, Langer T, Lukavsky P, Pechlaner C, Weissenberger H. 1996. On the bioisosteric potential of diazines: diazine analogues of the combined thromboxane A2 receptor antagonist and synthetase inhibitor Ridogrel. J Med Chem. 39:4058–4064.
  • Hibi S, Okamoto Y, Tagami K, Numata H, Kobayashi N, Shinoda M, Kawahara T, Harada K, Miyamoto K, Yamatsu I. 1996. Structure-activity relationships of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)-alkyl]-2-propenoic acid derivatives that inhibit both 5-lipoxygenase and thromboxane A2 synthetase. J Med Chem. 39:3148–3157.
  • Hiraku S, Taniguchi K, Wakitani K, Omawari N, Kira H, Miyamoto T, Okegawa T, Kawasaki A, Ujiie A. 1986. Pharmacological studies on the TXA2 synthetase inhibitor (E)-3-[p-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoic acid (OKY-046). Jpn J Pharmacol. 41:393–401.
  • Howes LG, James MJ, Florin T, Walker C. 2007. Nv-52: a novel thromboxane synthase inhibitor for the treatment of inflammatory bowel disease. Expert Opin Invest Drugs. 16:1255–1266.
  • Ihara H, Yokoyama C, Miyata A, Kosaka T, Nusing R, Ullrich V, Tanabe T. 1992. Induction of thromboxane synthase and prostaglandin endoperoxide synthase mRNAs in human erythroleukemia cells by phorbol ester. FEBS Lett. 306:161–164.
  • Jacobs C, Frotscher M, Dannhardt G, Hartmann RW. 2000. 1-Imidazolyl(alkyl)-substituted di- and tetrahydroquinolines and analogues: syntheses and evaluation of dual inhibitors of thromboxane A2 synthase and aromatase. J Med Chem. 43:1841–1851.
  • Jarrar YB, Shin JG, Lee SJ. 2013. Expression of arachidonic acid-metabolizing cytochrome P450s in human megakaryocytic Dami cells. In Vitro Cell Dev Biol Anim. 49:492–500.
  • Kajita S, Ruebel KH, Casey MB, Nakamura N, Lloyd RV. 2005. Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth. Modern Pathol. 18:221–227.
  • Kanda N, Kano R, Ishikawa T, Watanabe S. 2011. The antimycotic drugs itraconazole and terbinafine hydrochloride induce the production of human β-defensin-3 in human keratinocytes. Immunobiology. 216:497–504.
  • Kanda N, Watanabe S. 2006. Suppressive effects of antimycotics on tumor necrosis factor-alpha-induced CCL27, CCL2, and CCL5 production in human keratinocytes. Biochem Pharmacol. 72:463–473.
  • Kontogiorgis C, Hadjipavlou-Litina D. 2010. Thromboxane synthase inhibitors and thromboxane A2 receptor antagonists: a quantitative structure activity relationships (QSARs) analysis. Curr Med Chem. 17:3162–3214.
  • Liu XJ. 2015. Design, synthesis and evaluation of antiplatelet aggregation inhibitory activities of the analogs of picotamide. [accessed Sep 11]. Cardiovasc Hematol Agents Med Chem.
  • Michaux C, Dogne JM, Rolin S, Masereel B, Wouters J, Durant F. 2003. A pharmacophore model for sulphonyl-urea (-cyanoguanidine) compounds with dual action, thromboxane receptor antagonists and thromboxane synthase inhibitors. Eur J Med Chem. 38:703–710.
  • Michaux C, Rolin S, Dogne JM, Durant F, Masereel B, Delarge J, Wouters J. 2001. Structure determination and comparison of BM567, a sulfonylurea, with terbogrel, two compounds with dual action, thromboxane receptor antagonism and thromboxane synthase inhibition. Bioorg Med Chem Lett. 11:1019–1022.
  • Moon CH, Jung YS, Kim MH, Lee SH, Baik EJ, Park SW. 2000. Mechanism for antiplatelet effect of onion: AA release inhibition, thromboxane A2 synthase inhibition and TXA2/PGH2 receptor blockade. Prostaglandins Leukot Essent Fatty Acids. 62:277–283.
  • Moon YJ, Zhang S, Brazeau DA, Morris ME. 2007. Effects of the flavonoid biochanin A on gene expression in primary human hepatocytes and human intestinal cells. Mol Nutr Food Res. 51:317–323.
  • Moussa O, Riker JM, Klein J, Fraig M, Halushka PV, Watson DK. 2008. Inhibition of thromboxane synthase activity modulates bladder cancer cell responses to chemotherapeutic agents. Oncogene 27:55–62.
  • Muck S, Weber AA, Schror K. 1998. Effects of terbogrel on platelet function and prostaglandin endoperoxide transfer. Eur J Pharmacol. 344:45–48.
  • Nie D, Che M, Zacharek A, Qiao Y, Li L, Li X, Lamberti M, Tang K, Cai Y, Guo Y, et al. 2004. Differential expression of thromboxane synthase in prostate carcinoma: role in tumor cell motility. Am J Pathol. 164:429–439.
  • Oketani K, Nagakura N, Harada K, Inoue T. 2001. In vitro effects of E3040, a dual inhibitor of 5-lipoxygenase and thromboxane A2 synthetase, on eicosanoid production. Eur J Pharmacol. 422:209–216.
  • Onguru O, Scheithauer BW, Kovacs K, Vidal S, Jin L, Zhang S, Ruebel KH, Lloyd RV. 2004. Analysis of Cox-2 and thromboxane synthase expression in pituitary adenomas and carcinomas. Endocr Pathol. 15:17–27.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Rolin S, Dogne JM, Michaux C, Delarge J, Masereel B. 2001. Activity of a novel dual thromboxane A(2)receptor antagonist and thromboxane synthase inhibitor (BM-573) on platelet function and isolated smooth muscles. Prostaglandins Leukot Essent Fatty Acids. 65:67–72.
  • Rolin S, Dogne JM, Vastersaegher C, Hanson J, Masereel B. 2004. Pharmacological evaluation of both enantiomers of (R,S)-BM-591 as thromboxane A2 receptor antagonists and thromboxane synthase inhibitors. Prostaglandins Other Lipid Mediat. 74:75–86.
  • Rowe J, Campbell S, Gallery ED. 2000. Effects of hypoxia on regulation of prostanoid production in decidual endothelial cells in normal and preeclamptic pregnancy. J Soc Gynecol Invest. 7:118–124.
  • Saareks V, Mucha I, Sievi E, Vapaatalo H, Riutta A. 1998. Nicotine stereoisomers and cotinine stimulate prostaglandin E2 but inhibit thromboxane B2 and leukotriene E4 synthesis in whole blood. Eur J Pharmacol. 353:87–92.
  • Sakai H, Suzuki T, Takahashi Y, Ukai M, Tauchi K, Fujii T, Horikawa N, Minamimura T, Tabuchi Y, Morii M, et al. 2006. Upregulation of thromboxane synthase in human colorectal carcinoma and the cancer cell proliferation by thromboxane A2. FEBS Lett. 580:3368–3374.
  • Schuster I, Bernhardt R. 2007. Inhibition of cytochromes P450: existing and new promising therapeutic targets. Drug Metab Rev. 39:481–499.
  • Sekhar PN, Reddy LA, De Maeyer M, Kumar KP, Srinivasulu YS, Sunitha MS, Sphoorthi IS, Jayasree G, Rao AM, Kothekar VS, et al. 2009. Genome wide analysis and comparative docking studies of new diaryl furan derivatives against human cyclooxygenase-2, lipoxygenase, thromboxane synthase and prostacyclin synthase enzymes involved in inflammatory pathway. J Mol Graph Model. 28:313–329.
  • Soyka R, Guth BD, Weisenberger HM, Luger P, Muller TH. 1999. Guanidine derivatives as combined thromboxane A2 receptor antagonists and synthase inhibitors. J Med Chem. 42:1235–1249.
  • Soyka R, Heckel A, Nickl J, Eisert W, Muller TH, Weisenberger H. 1994. 6,6-Disubstituted hex-5-enoic acid derivatives as combined thromboxane A2 receptor antagonists and synthetase inhibitors. J Med Chem. 37:26–39.
  • Steinhilber D, Jaschonek K, Knospe J, Morof O, Roth HJ. 1990. Effects of novel antifungal azole derivatives on the 5-lipoxygenase and cyclooxygenase pathway. Arzneimittelforschung. 40:1260–1263.
  • Takeuchi K, Kohn TJ, True TA, Mais DE, Wikel JH, Utterback BG, Wyss VL, Jakubowski JA. 1998. Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 3. Synthesis and biological activities of oxazolecarboxamide-substituted ω-phenyl-ω-(3-pyridyl)alkenoic acid derivatives and related compounds. J Med Chem. 41:5362–5374.
  • Trochtenberg DS, Lefferts PL, King GA, Hwang YS, Christman BW, Snapper JR. 1992. Effects of thromboxane synthase and cyclooxygenase inhibition on PAF-induced changes in lung function and arachidonic acid metabolism. Prostaglandins. 44:555–577.
  • Tubaro E, Belogi L, Mezzadri CM. 1996. Antiplatelet effect of a new inhibitor of thromboxane synthase and thromboxane A2 receptors. Arzneimittelforschung. 46:35–41.
  • Uematsu T, Kosuge K, Umemura K, Nakano M, Terakawa M, Nakashima M. 1996. Pharmacokinetic and pharmacodynamic properties of FK070 (KDI-792), a novel thromboxane receptor antagonist/thromboxane synthetase inhibitor, after single and multiple oral administrations to healthy volunteers. J Pharm Pharmacol. 48:380–385.
  • Ullrich V, Hecker M. 1990. A concept for the mechanism of prostacyclin and thromboxane A2 biosynthesis. Adv Prostaglandin Thromboxane Leukot Res. 20:95–101.
  • Wachter GA, Hartmann RW, Sergejew T, Grun GL, Ledergerber D. 1996. Tetrahydronaphthalenes: Influence of heterocyclic substituents on inhibition of steroid enzymes P450arom and P45017. J Med Chem. 39:834–841.
  • Wang LH, Matijevic-Aleksic N, Hsu PY, Ruan KH, Wu KK, Kulmacz RJ. 1996. Identification of thromboxane A2 synthase active site residues by molecular modeling-guided site-directed mutagenesis. J Biol Chem. 271:19970–19975.
  • Yagi A, Kabash A, Mizuno K, Moustafa SM, Khalifa TI, Tsuji H. 2003. Radical scavenging glycoprotein inhibiting cyclooxygenase-2 and thromboxane A2 synthase from Aloe vera gel. Planta Med. 69:269–271.
  • Yeh HC, Tsai AL, Wang LH. 2007. Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases. Arch Biochem Biophys. 461:159–168.
  • Yokoyama C, Miyata A, Ihara H, Ullrich V, Tanabe T. 1991. Molecular cloning of human platelet thromboxane A synthase. Biochem Biophys Res Commun. 178:1479–1484.
  • Yu SM, Wu TS, Teng CM. 1994. Pharmacological characterization of cinnamophilin, a novel dual inhibitor of thromboxane synthase and thromboxane A2 receptor. Brit J Pharmacol. 111:906–912.

References

  • Bachschmid M, Schildknecht S, Ullrich V. 2005. Redox regulation of vascular prostanoid synthesis by the nitric oxide-superoxide system. Biochem Biophys Res Commun. 338:536–542.
  • Camacho M, Rodriguez C, Guadall A, Alcolea S, Orriols M, Escudero JR, Martinez-Gonzalez J, Vila L. 2011. Hypoxia upregulates PGI-synthase and increases PGI2 release in human vascular cells exposed to inflammatory stimuli. J Lipid Res. 52:720–731.
  • Camacho M, Rodriguez C, Salazar J, Martinez-Gonzalez J, Ribalta J, Escudero JR, Masana L, Vila L. 2008. Retinoic acid induces PGI synthase expression in human endothelial cells. J Lipid Res. 49:1707–1714.
  • Cathcart MC, Reynolds JV, O'Byrne KJ, Pidgeon GP. 2010. The role of prostacyclin synthase and thromboxane synthase signaling in the development and progression of cancer. Biochim Biophys Acta. 1805:153–166.
  • Chao WC, Lu JF, Wang JS, Yang HC, Chen HH, Lan YK, Yu YC, Chou PT, Wang LH. 2011. Probing the interaction between prostacyclin synthase and prostaglandin H2 analogues or inhibitors via a combination of resonance Raman spectroscopy and molecular dynamics simulation approaches. J Am Chem Soc. 133:18870–18879.
  • Chiang CW, Yeh HC, Wang LH, Chan NL. 2006. Crystal structure of the human prostacyclin synthase. J Mol Biol. 364:266–274.
  • Ding ZQ, Rowe J, Ng B, Sinosich MJ, Gallery ED. 2002. Modulation of prostacyclin and thromboxane secretion by cytotrophoblasts from normal and pre-eclamptic human pregnancies. Placenta. 23:594–599.
  • Graf H, Ruf HH, Ullrich V. 1983. Prostacyclin synthase, a cytochrome P450 enzyme. Angew Chem Int Ed. 22:487–488.
  • Griffoni C, Spisni E, Strillacci A, Toni M, Bachschmid MM, Tomasi V. 2007. Selective inhibition of prostacyclin synthase activity by rofecoxib. J Cell Mol Med. 11:327–338.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Hecker M, Ullrich V. 1989. On the mechanism of prostacyclin and thromboxane A2 biosynthesis. J Biol Chem. 264:141–150.
  • Korita D, Itoh H, Sagawa N, Yura S, Yoshida M, Kakui K, Takemura M, Fujii S. 2004. 17β-Estradiol up-regulates prostacyclin production in cultured human uterine myometrial cells via augmentation of both cyclooxygenase-1 and prostacyclin synthase expression. J Soc Gynecol Invest. 11:457–464.
  • Korita D, Sagawa N, Itoh H, Yura S, Yoshida M, Kakui K, Takemura M, Yokoyama C, Tanabe T, Fujii S. 2002. Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression. J Clin Endocrinol Metab. 87:5209–5219.
  • Li YC, Chiang CW, Yeh HC, Hsu PY, Whitby FG, Wang LH, Chan NL. 2008. Structures of prostacyclin synthase and its complexes with substrate analog and inhibitor reveal a ligand-specific heme conformation change. J Biol Chem. 283:2917–2926.
  • Mao JT, Smoake J, Park HK, Lu QY, Xue B. 2016. Grape seed procyanidin extract mediates antineoplastic effects against lung cancer via modulations of prostacyclin and 15-HETE eicosanoid pathways. Cancer Prev Res. 9:925–932.
  • Miyata A, Hara S, Yokoyama C, Inoue H, Ullrich V, Tanabe T. 1994. Molecular cloning and expression of human prostacyclin synthase. Biochem Biophys Res Commun. 200:1728–1734.
  • Nakayama T. 2010. Genetic polymorphisms of prostacyclin synthase gene and cardiovascular disease. Int Angiol. 29(2 Suppl):33–42.
  • Okahara K, Sun B, Kambayashi J. 1998. Upregulation of prostacyclin synthesis-related gene expression by shear stress in vascular endothelial cells. Arteriosclerosis Thrombosis Vascul Biol. 18:1922–1926.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Sharanek A, Burban A, Humbert L, Bachour-El Azzi P, Felix-Gomes N, Rainteau D, Guillouzo A. 2015. Cellular accumulation and toxic effects of bile acids in cyclosporine A-treated HepaRG hepatocytes. Toxicol Sci. 147:573–587.
  • Skogastierna C, Björkhem-Bergman L, Bergman P, Eliasson E, Rane A, Ekstrom L. 2013. Influence of simvastatin on the thromboxane and prostacyclin pathways, in vitro and in vivo. J Cardiovasc Pharmacol. 61:1–7.
  • Tan X, Poulose EM, Raveendran VV, Zhu BT, Stechschulte DJ, Dileepan KN. 2011. Regulation of the expression of cyclooxygenases and production of prostaglandin I2 and E2 in human coronary artery endothelial cells by curcumin. J Physiol Pharmacol. 62:21–28.
  • Ullrich V, Hecker M. 1990. A concept for the mechanism of prostacyclin and thromboxane A2 biosynthesis. Adv Prostaglandin Thromboxane Leukot Res. 20:95–101.
  • Wada M, Yokoyama C, Hatae T, Shimonishi M, Nakamura M, Imai Y, Ullrich V, Tanabe T. 2004. Purification and characterization of recombinant human prostacyclin synthase. J Biochem. 135:455–463.
  • Wang J, Ikeda R, Che XF, Ooyama A, Yamamoto M, Furukawa T, Hasui K, Zheng CL, Tajitsu Y, Oka T, et al. 2013. VEGF expression is augmented by hypoxia-induced PGIS in human fibroblasts. Int J Oncol. 43:746–754.
  • Yeh HC, Hsu PY, Wang JS, Tsai AL, Wang LH. 2005. Characterization of heme environment and mechanism of peroxide bond cleavage in human prostacyclin synthase. Biochim Biophys Acta. 1738:121–132.
  • Yeh HC, Tsai AL, Wang LH. 2007. Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human prostacyclin and thromboxane synthases. Arch Biochem Biophys. 461:159–168.

References

  • Auchus RJ. 2017. Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. J Steroid Biochem Mol Biol. 165:71–78.
  • Auchus RJ, Miller WL. 2015. Chapter 12, P450 enzymes in steroid processing. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 851–879.
  • Nebert DW, Russell DW. 2002. Clinical importance of the cytochromes P450. Lancet. 360:1155–1162.

References

  • Acimovic J, Goyal S, Kosir R, Golicnik M, Perse M, Belic A, Urlep Z, Guengerich FP, Rozman D. 2016. Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis. Sci Rep. 6:28462.
  • An S, Jang YS, Park JS, Kwon BM, Paik YK, Jeong TS. 2008. Inhibition of acyl-coenzyme A:cholesterol acyltransferase stimulates cholesterol efflux from macrophages and stimulates farnesoid X receptor in hepatocytes. Exp Mol Med. 40:407–417.
  • Andreou ER, Prokipcak RD. 1998. Analysis of human CYP7A1 mRNA decay in HepG2 cells by reverse transcription-polymerase chain reaction. Arch Biochem Biophys. 357:137–146.
  • Axelson M, Sjövall J. 1990. Potential bile acid precursors in plasma–possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man. J Steroid Biochem. 36:631–640.
  • Björkhem I. 1992. Mechanism of degradation of the steroid side chain in the formation of bile acids. J Lipid Res. 33:455–471.
  • Björkhem I, Diczfalusy U, Lovgren-Sandblom A, Starck L, Jonsson M, Tallman K, Schirmer H, Ousager LB, Crick PJ, Wang Y, et al. 2014. On the formation of 7-ketocholesterol from 7-dehydrocholesterol in patients with CTX and SLO. J Lipid Res. 55:1165–1172.
  • Charoenteeraboon J, Nithipatikom K, Campbell WB, Piyachaturawat P, Wilairat P, Rongnoparut P. 2005. Induction of human cholesterol 7α-hydroxylase in HepG2 cells by 2,4,6-trihydroxyacetophenone. Eur J Pharmacol. 515:43–46.
  • Chen W, Owsley E, Yang Y, Stroup D, Chiang JY. 2001. Nuclear receptor-mediated repression of human cholesterol 7α-hydroxylase gene transcription by bile acids. J Lipid Res. 42:1402–1412.
  • Chiang JY, Kimmel R, Weinberger C, Stroup D. 2000. Farnesoid X receptor responds to bile acids and represses cholesterol 7α-hydroxylase gene (CYP7A1) transcription. J Biol Chem. 275:10918–10924.
  • Davalos A, Fernandez-Hernando C, Cerrato F, Martinez-Botas J, Gomez-Coronado D, Gomez-Cordoves C, Lasuncion MA. 2006. Red grape juice polyphenols alter cholesterol homeostasis and increase LDL-receptor activity in human cells in vitro. J Nutr. 136:1766–1773.
  • Drover VA, Agellon LB. 2004. Regulation of the human cholesterol 7α-hydroxylase gene (CYP7A1) by thyroid hormone in transgenic mice. Endocrinology. 145:574–581.
  • Drover VA, Wong NC, Agellon LB. 2002. A distinct thyroid hormone response element mediates repression of the human cholesterol 7α-hydroxylase (CYP7A1) gene promoter. Mol Endocrinol. 16:14–23.
  • Ellis E, Axelson M, Abrahamsson A, Eggertsen G, Thorne A, Nowak G, Ericzon BG, Björkhem I, Einarsson C. 2003. Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor. Hepatology. 38:930–938.
  • Ellis EC. 2006. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes. World J Gastroenterol. 12:4640–4645.
  • Fan P, Zhang B, Kuroki S, Saku K. 2004. Pitavastatin, a potent hydroxymethylglutaryl coenzyme a reductase inhibitor, increases cholesterol 7α-hydroxylase gene expression in HepG2 cells. Circ J. 68:1061–1066.
  • Gbaguidi GF, Agellon LB. 2004. The inhibition of the human cholesterol 7α-hydroxylase gene (CYP7A1) promoter by fibrates in cultured cells is mediated via the liver X receptor α and peroxisome proliferator-activated receptor α heterodimer. Nucl Acids Res. 32:1113–1121.
  • Gerbod-Giannone MC, Del Castillo-Olivares A, Janciauskiene S, Gil G, Hylemon PB. 2002. Suppression of cholesterol 7α-hydroxylase transcription and bile acid synthesis by an α1-antitrypsin peptide via interaction with α1-fetoprotein transcription factor. J Biol Chem. 277:42973–42980.
  • Gonzalez R, Cruz A, Ferrin G, Lopez-Cillero P, Briceno J, Gomez MA, Rufian S, Padillo J, De la Mata M, Marin JJ, et al. 2011. Cytoprotective properties of rifampicin are related to the regulation of detoxification system and bile acid transporter expression during hepatocellular injury induced by hydrophobic bile acids. J Hepatobiliary Pancreat Sci. 18:740–750.
  • Gonzalez R, Cruz A, Ferrin G, Lopez-Cillero P, Fernandez-Rodriguez R, Briceno J, Gomez MA, Rufian S, Mata Mde L, Martinez-Ruiz A, et al. 2011. Nitric oxide mimics transcriptional and post-translational regulation during α-tocopherol cytoprotection against glycochenodeoxycholate-induced cell death in hepatocytes. J Hepatol. 55:133–144.
  • Goodwin B, Watson MA, Kim H, Miao J, Kemper JK, Kliewer SA. 2003. Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-α. Mol Endocrinol. 17:386-394.
  • Guo J, Gao Y, Cao X, Zhang J, Chen W. 2017. Cholesterol-lowing effect of taurine in HepG2 cell. Lipids Health Dis. 16:56.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Hofman MK, Groenendijk M, Verkuijlen PJ, Jonkers IJ, Mohrschladt MF, Smelt AH, Princen HM. 2004. Modulating effect of the A-278C promoter polymorphism in the cholesterol 7α-hydroxylase gene on serum lipid levels in normolipidaemic and hypertriglyceridaemic individuals. Eur J Human Genet. 12:935–941.
  • Honda A, Ikegami T, Nakamuta M, Miyazaki T, Iwamoto J, Hirayama T, Saito Y, Takikawa H, Imawari M, Matsuzaki Y. 2013. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepatology. 57:1931–1941.
  • Horton JD, Cuthbert JA, Spady DK. 1995. Regulation of hepatic 7α-hydroxylase expression and response to dietary cholesterol in the rat and hamster. J Biol Chem. 270:5381-5387.
  • Jahan A, Chiang JY. 2005. Cytokine regulation of human sterol 12α-hydroxylase (CYP8B1) gene. Am J Physiol Gastrointest Liver Physiol. 288:G685–695.
  • Janowski BA, Grogan MJ, Jones SA, Wisely GB, Kliewer SA, Corey EJ, Mangelsdorf DJ. 1999. Structural requirements of ligands for the oxysterol liver X receptors LXRα and LXRβ. Proc Natl Acad Sci USA. 96:266–271.
  • Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. 1996. An oxysterol signalling pathway mediated by the nuclear receptor LXRα. Nature. 383:728–731.
  • Jelinek DF, Andersson S, Slaughter CA, Russell DW. 1990. Cloning and regulation of cholesterol 7α-hydroxylase, the rate-limiting enzyme in bile acid biosynthesis. J Biol Chem. 265:8190–8197.
  • Jonkers IJ, Smelt AH, Princen HM, Kuipers F, Romijn JA, Boverhof R, Masclee AA, Stellaard F. 2006. Fish oil increases bile acid synthesis in male patients with hypertriglyceridemia. J Nutr. 136:987–991.
  • Lala DS, Syka PM, Lazarchik SB, Mangelsdorf DJ, Parker KL, Heyman RA. 1997. Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. Proc Natl Acad Sci USA. 94:4895–4900.
  • Lammel Lindemann JA, Angajala A, Engler DA, Webb P, Ayers SD. 2014. Thyroid hormone induction of human cholesterol 7α-hydroxylase (Cyp7a1) in vitro. Mol Cell Endocrinol. 388:32–40.
  • Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, Sundseth SS, Winegar DA, Blanchard DE, Spencer TA, et al. 1997. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem. 272:3137–3140.
  • Lee EJ, Kim MH, Kim YR, Park JW, Park WJ. 2018. Proteasome inhibition protects against diet-induced gallstone formation through modulation of cholesterol and bile acid homeostasis. Int J Mol Med. 41:1715–1723.
  • Leng E, Xiao Y, Mo Z, Li Y, Zhang Y, Deng X, Zhou M, Zhou C, He Z, He J, Xiao L, Li J, Li W. 2018. Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells. BMC Complement Altern Med. 18:122.
  • Li Q, Yin W, Cai M, Liu Y, Hou H, Shen Q, Zhang C, Xiao J, Hu X, Wu Q, et al. 2010. NO-1886 suppresses diet-induced insulin resistance and cholesterol accumulation through STAT5-dependent upregulation of IGF1 and CYP7A1. J Endocrinol. 204:47–56.
  • Li T, Chanda D, Zhang Y, Choi HS, Chiang JY. 2010. Glucose stimulates cholesterol 7α-hydroxylase gene transcription in human hepatocytes. J Lipid Res. 51:832–842.
  • Li T, Francl JM, Boehme S, Ochoa A, Zhang Y, Klaassen CD, Erickson SK, Chiang JY. 2012. Glucose and insulin induction of bile acid synthesis: mechanisms and implication in diabetes and obesity. J Biol Chem. 287:1861–1873.
  • Li T, Jahan A, Chiang JY. 2006. Bile acids and cytokines inhibit the human cholesterol 7α-hydroxylase gene via the JNK/c-jun pathway in human liver cells. Hepatology (Baltimore) 43:1202–1210.
  • Li T, Kong X, Owsley E, Ellis E, Strom S, Chiang JY. 2006. Insulin regulation of cholesterol 7α-hydroxylase expression in human hepatocytes: roles of forkhead box O1 and sterol regulatory element-binding protein 1c. J Biol Chem. 281:28745–28754.
  • Li YC, Chiang JYL. 1991. The expression of a catalytically active cholesterol 7α-hydroxylase cytochrome P-450 in Escherichia coli. J Biol Chem. 266:19186–19191.
  • Liu D, Yang A, Wu C, Guo P, Proksch P, Lin W. 2014. Lipid-lowering effects of farnesylquinone and related analogues from the marine-derived Streptomyces nitrosporeus. Bioorg Med Chem Lett. 24:5288–5293.
  • Liu J, Lu H, Lu YF, Lei X, Cui JY, Ellis E, Strom SC, Klaassen CD. 2014. Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 141:538–546.
  • Marrapodi M, Chiang JY. 2000. Peroxisome proliferator-activated receptor α (PPARα) and agonist inhibit cholesterol 7α-hydroxylase gene (CYP7A1) transcription. J Lipid Res. 41:514–520.
  • Morikawa K, Kondo I, Kanamaru Y, Nagaoka S. 2007. A novel regulatory pathway for cholesterol degradation via lactostatin. Biochem Biophys Res Commun. 352:697–702.
  • Nguyen LB, Shefer S, Salen G, Tint SG, Batta AK. 1998. Competitive inhibition of hepatic sterol 27-hydroxylase by sitosterol: decreased activity in sitosterolemia. Proc Assoc Am Physicians. 110:32–39.
  • Norlin M, Andersson U, Björkhem I, Wikvall K. 2000. Oxysterol 7α-hydroxylase activity by cholesterol 7α-hydroxylase (CYP7A). J Biol Chem. 275:34046–34053.
  • Norlin M, Toll A, Björkhem I, Wikvall K. 2000. 24-Hydroxycholesterol is a substrate for hepatic cholesterol 7α-hydroxylase (CYP7A). J Lipid Res. 41:1629–1639.
  • Norlin M, Wikvall K. 2007. Enzymes in the conversion of cholesterol into bile acids. Curr Mol Med. 7:199–218.
  • Ogishima T, Deguchi S, Okuda K. 1987. Purification and characterization of cholesterol 7α-hydroxylase from rat liver microsomes. J Biol Chem. 262:7646–7650.
  • Owsley E, Chiang JY. 2003. Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7α-hydroxylase gene. Biochem Biophys Res Commun. 304:191–195.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Parker RA, Garcia R, Ryan CS, Liu X, Shipkova P, Livanov V, Patel P, Ho SP. 2013. Bile acid and sterol metabolism with combined HMG-CoA reductase and PCSK9 suppression. J Lipid Res. 54:2400–2409.
  • Roglans N, Vazquez-Carrera M, Alegret M, Novell F, Zambon D, Ros E, Laguna JC, Sanchez RM. 2004. Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients. Eur J Clin Pharmacol. 59:855–861.
  • Russell DW. 1999. Nuclear orphan receptors control cholesterol catabolism. Cell. 97:539–542.
  • Schroepfer GJ, Jr. 2000. Oxysterols: modulators of cholesterol metabolism and other processes. Physiol Rev. 80:361–554.
  • Sharanek A, Burban A, Humbert L, Bachour-El Azzi P, Felix-Gomes N, Rainteau D, Guillouzo A. 2015. Cellular accumulation and toxic effects of bile acids in cyclosporine A-treated HepaRG hepatocytes. Toxicol Sci. 147:573–587.
  • Shinkyo R, Guengerich FP. 2011. Cytochrome P450 7A1 cholesterol 7α-hydroxylation: individual reaction steps in the catalytic cycle and rate-limiting ferric iron reduction. J Biol Chem. 286:4632–4643.
  • Shinkyo R, Xu L, Tallman KA, Cheng Q, Porter NA, Guengerich FP. 2011. Conversion of 7-dehydrocholesterol to 7-ketocholesterol is catalyzed by human cytochrome P450 7A1 and occurs by direct oxidation without an epoxide intermediate. J Biol Chem. 286:33021–33028.
  • Smelt AH. 2010. Triglycerides and gallstone formation. Clin Chim Acta. 411:1625–1631.
  • Song KH, Chiang JY. 2006. Glucagon and cAMP inhibit cholesterol 7α-hydroxylase (CYP7A1) gene expression in human hepatocytes: discordant regulation of bile acid synthesis and gluconeogenesis. Hepatology. 43:117–125.
  • Song Y, Xu C, Shao S, Liu J, Xing W, Xu J, Qin C, Li C, Hu B, Yi S, et al. 2015. Thyroid-stimulating hormone regulates hepatic bile acid homeostasis via SREBP-2/HNF-4α/CYP7A1 axis. J Hepatol. 62:1171–1179.
  • Taniguchi T, Chen J, Cooper AD. 1994. Regulation of cholesterol 7α-hydroxylase gene expression in HepG2 cells. Effect of serum, bile salts, and coordinate and noncoordinate regulation with other sterol-responsive genes. J Biol Chem. 269:10071–10078.
  • Tempel W, Grabovec I, MacKenzie F, Dichenko YV, Usanov SA, Gilep AA, Park HW, Strushkevich N. 2014. Structural characterization of human cholesterol 7α-hydroxylase. J Lipid Res. 55:1925–1932.
  • Wang DP, Stroup D, Marrapodi M, Crestani M, Galli G, Chiang JY. 1996. Transcriptional regulation of the human cholesterol 7α-hydroxylase gene (CYP7A) in HepG2 cells. J Lipid Res. 37:1831–1841.
  • Waterman MR, John ME, Simpson ER. 1986. Regulation of synthesis and activity of cytochrome P-450 enzymes in physiological pathways. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism and biochemistry, 2nd Ed. New York (NY): Plenum Press; p. 345–386.
  • Wu Z, Chiang JY. 2001. Transcriptional regulation of human oxysterol 7α-hydroxylase gene (CYP7B1) by Sp1. Gene. 272(1-2):191-197.
  • Zak A, Zeman M, Hrubant K, Vecka M, Tvrzicka E. 2007. Effect of hypolipidemic treatment on the composition of bile and the risk or cholesterol gallstone disease. Cas Lek Cesk. 146:24–34. Czech.
  • Zhang JM, Wang XH, Hao LH, Wang H, Zhang XY, Muhammad I, Qi Y, Li GL, Sun XQ. 2017. Nrf2 is crucial for the down-regulation of Cyp7a1 induced by arachidonic acid in Hepg2 cells. Environ Toxicol Pharmacol. 52:21–26.
  • Zhang T, Zhao M, Lu D, Wang S, Yu F, Guo L, Wen S, Wu B. 2018. REV-ERBα regulates CYP7A1 through repression of liver receptor homolog-1. Drug Metab Dispos. 46:248–258.
  • Zhang Y, Jackson JP, St Claire RL 3rd, Freeman K, Brouwer KR, Edwards JE. 2017. Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes. Pharmacol Res Perspect. 5(4):e00329. DOI:10.1002/prp2.329

References

  • An S, Jang YS, Park JS, Kwon BM, Paik YK, Jeong TS. 2008. Inhibition of acyl-coenzyme A:cholesterol acyltransferase stimulates cholesterol efflux from macrophages and stimulates farnesoid X receptor in hepatocytes. Exp Mol Med. 40:407–417.
  • Dulos J, Boots AH. 2006. DHEA metabolism in arthritis: a role for the P450 enzyme Cyp7b at the immune-endocrine crossroad. Ann NY Acad Sci. 1069:401–413.
  • Dulos J, Kaptein A, Kavelaars A, Heijnen C, Boots A. 2005. Tumour necrosis factor-α stimulates dehydroepiandrosterone metabolism in human fibroblast-like synoviocytes: a role for nuclear factor-κB and activator protein-1 in the regulation of expression of cytochrome P450 enzyme 7b. Arthritis Res Ther. 7:R1271–1280.
  • Dulos J, van der Vleuten MA, Kavelaars A, Heijnen CJ, Boots AM. 2005. CYP7B expression and activity in fibroblast-like synoviocytes from patients with rheumatoid arthritis: regulation by proinflammatory cytokines. Arthritis Rheum. 52:770–778.
  • Ellis EC. 2006. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes. World J Gastroenterol. 12:4640–4645.
  • Kim B, Moon JY, Choi MH, Yang HH, Lee S, Lim KS, Yoon SH, Yu KS, Jang IJ, Cho JY. 2013. Global metabolomics and targeted steroid profiling reveal that rifampin, a strong human PXR activator, alters endogenous urinary steroid markers. J Proteome Res. 12:1359–1368.
  • Kim SB, Chalbot S, Pompon D, Jo DH, Morfin R. 2004. The human cytochrome P450 7B1: catalytic activity studies. J Steroid Biochem Mol Biol. 92:383–389.
  • Lutz SZ, Hennenlotter J, Scharpf MO, Sailer C, Fritsche L, Schmid V, Kantartzis K, Wagner R, Lehmann R, Berti L, et al. 2018. Androgen receptor overexpression in prostate cancer in type 2 diabetes. Mol Metab. 8:158–166.
  • Olsson M, Gustafsson O, Skogastierna C, Tolf A, Rietz BD, Morfin R, Rane A, Ekstrom L. 2007. Regulation and expression of human CYP7B1 in prostate: overexpression of CYP7B1 during progression of prostatic adenocarcinoma. Prostate. 67:1439–1446.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Pettersson H, Holmberg L, Axelson M, Norlin M. 2008. CYP7B1-mediated metabolism of dehydroepiandrosterone and 5α-androstane-3β,17β-diol–potential role(s) for estrogen signaling. FEBS J. 275:1778–1789.
  • Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M, Russell DW, Björkhem I, Seckl J, Lathe R. 1997. Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7α-hydroxy dehydroepiandrosterone and 7α-hydroxy pregnenolone. Proc Natl Acad Sci USA. 94:4925–4930.
  • Schwarz M, Lund EG, Lathe R, Björkhem I, Russell DW. 1997. Identification and characterization of a mouse oxysterol 7α-hydroxylase cDNA. J Biol Chem. 272:23995-24001.
  • Steckelbroeck S, Watzka M, Lutjohann D, Makiola P, Nassen A, Hans VH, Clusmann H, Reissinger A, Ludwig M, Siekmann L, et al. 2002. Characterization of the dehydroepiandrosterone (DHEA) metabolism via oxysterol 7α-hydroxylase and 17-ketosteroid reductase activity in the human brain. J Neurochem. 83:713–726.
  • Stiles AR, McDonald JG, Bauman DR, Russell DW. 2009. CYP7B1: One cytochrome P450, two human genetic diseases, and multiple physiological functions. J Biol Chem. 284:28485–28489.
  • Sumantran VN, Mishra P, Bera R, Sudhakar N. 2016. Microarray analysis of differentially-expressed genes encoding CYP450 and Phase II drug metabolizing enzymes in psoriasis and melanoma. Pharmaceutics. 8. DOI:10.3390/pharmaceutics8010004
  • Tang W, Eggertsen G, Chiang JY, Norlin M. 2006. Estrogen-mediated regulation of CYP7B1: a possible role for controlling DHEA levels in human tissues. J Steroid Biochem Mol Biol. 100:42–51.
  • Wu Q, Ishikawa T, Sirianni R, Tang H, McDonald JG, Yuhanna IS, Thompson B, Girard L, Mineo C, Brekken RA, et al. 2013. 27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth. Cell Rep. 5:637–645.
  • Yantsevich AV, Dichenko YV, Mackenzie F, Mukha DV, Baranovsky AV, Gilep AA, Usanov SA, Strushkevich NV. 2014. Human steroid and oxysterol 7α-hydroxylase CYP7B1: substrate specificity, azole binding and misfolding of clinically relevant mutants. FEBS J. 281:1700–1713.

References

  • Andersson U, Yang YZ, Björkhem I, Einarsson C, Eggertsen G, Gafvels M. 1999. Thyroid hormone suppresses hepatic sterol 12α-hydroxylase (CYP8B1) activity and messenger ribonucleic acid in rat liver: failure to define known thyroid hormone response elements in the gene. Biochim Biophys Acta. 1438:167–174.
  • Andreou ER, Prokipcak RD. 1998. Analysis of human CYP7A1 mRNA decay in HepG2 cells by reverse transcription-polymerase chain reaction. Arch Biochem Biophys. 357:137–146.
  • Antherieu S, Bachour-El Azzi P, Dumont J, Abdel-Razzak Z, Guguen-Guillouzo C, Fromenty B, Robin MA, Guillouzo A. 2013. Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells. Hepatology. 57:1518–1529.
  • Chiang JY. 2004. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J Hepatol. 40:539–551.
  • Ellis E, Axelson M, Abrahamsson A, Eggertsen G, Thorne A, Nowak G, Ericzon BG, Björkhem I, Einarsson C. 2003. Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor. Hepatology. 38:930–938.
  • Ellis EC. 2006. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes. World J Gastroenterol. 12:4640–4645.
  • Gafvels M, Olin M, Chowdhary BP, Raudsepp T, Andersson U, Persson B, Jansson M, Björkhem I, Eggertsen G. 1999. Structure and chromosomal assignment of the sterol 12α-hydroxylase gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid of introns. Genomics. 56:184–196.
  • Jahan A, Chiang JY. 2005. Cytokine regulation of human sterol 12α-hydroxylase (CYP8B1) gene. Am J Physiol Gastrointest Liver Physiol. 288:G685–695.
  • Li Y, Mezei O, Shay NF. 2007. Human and murine hepatic sterol-12α-hydroxylase and other xenobiotic metabolism mRNA are upregulated by soy isoflavones. J Nutr. 137:1705–1712.
  • Mörk LM, Strom SC, Mode A, Ellis EC. 2016. Addition of dexamethasone alters the bile acid composition by inducing CYP8B1 in primary cultures of human hepatocytes. J Clin Exp Hepatol. 6:87–93.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Parker RA, Garcia R, Ryan CS, Liu X, Shipkova P, Livanov V, Patel P, Ho SP. 2013. Bile acid and sterol metabolism with combined HMG-CoA reductase and PCSK9 suppression. J Lipid Res. 54:2400–2409.
  • Pathak P, Li T, Chiang JY. 2013. Retinoic acid-related orphan receptor α regulates diurnal rhythm and fasting induction of sterol 12α-hydroxylase in bile acid synthesis. J Biol Chem. 288:37154–37165.
  • Pikuleva IA. 2006. Cytochrome P450s and cholesterol homeostasis. Pharmacol Ther. 112:761–773.
  • Russell DW. 2003. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 72:137–174.
  • Sharanek A, Burban A, Humbert L, Bachour-El Azzi P, Felix-Gomes N, Rainteau D, Guillouzo A. 2015. Cellular accumulation and toxic effects of bile acids in cyclosporine A-treated HepaRG hepatocytes. Toxicol Sci. 147:573–587.
  • Zhang M, Chiang JY. 2001. Transcriptional regulation of the human sterol 12α-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4α in mediating bile acid repression. J Biol Chem. 276:41690–41699.

References

  • Acimovic J, Goyal S, Kosir R, Golicnik M, Perse M, Belic A, Urlep Z, Guengerich FP, Rozman D. 2016. Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis. Sci Rep. 6:28462.
  • Asif AR, Ljubojevic M, Sabolic I, Shnitsar V, Metten M, Anzai N, Muller GA, Burckhardt G, Hagos Y. 2006. Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells. Am J Physiol Endocrinol Metab. 291:E1351–1359.
  • Aumo L, Rusten M, Mellgren G, Bakke M, Lewis AE. 2010. Functional roles of protein kinase A (PKA) and exchange protein directly activated by 3´,5´-cyclic adenosine 5'-monophosphate (cAMP) 2 (EPAC2) in cAMP-mediated actions in adrenocortical cells. Endocrinology. 151:2151–2161.
  • Babischkin JS, Grimes RW, Pepe GJ, Albrecht ED. 1997. Estrogen stimulation of P450 cholesterol side-chain cleavage activity in cultures of human placental syncytiotrophoblasts. Biol Reprod. 56:272–278.
  • Boe AS, Bredholt G, Knappskog PM, Hjelmervik TO, Mellgren G, Winqvist O, Kampe O, Husebye ES. 2004. Autoantibodies against 21-hydroxylase and side-chain cleavage enzyme in autoimmune Addison's disease are mainly immunoglobulin G1. Eur J Endocrinol. 150:49–56.
  • Breckwoldt M, Selvaraj N, Aharoni D, Barash A, Segal I, Insler V, Amsterdam A. 1996. Expression of Ad4-BP/cytochrome P450 side chain cleavage enzyme and induction of cell death in long-term cultures of human granulosa cells. Mol Human Reprod. 2:391–400.
  • Chen S, Sawicka J, Betterle C, Powell M, Prentice L, Volpato M, Rees Smith B, Furmaniak J. 1996. Autoantibodies to steroidogenic enzymes in autoimmune polyglandular syndrome, Addison's disease, and premature ovarian failure. J Clin Endocrinol Metab. 81:1871–1876.
  • Davydov R, Strushkevich N, Smil D, Yantsevich A, Gilep A, Usanov S, Hoffman BM. 2015. Evidence that Compound I is the active species in both the hydroxylase and lyase steps by which P450scc converts cholesterol to pregnenolone: EPR/ENDOR/cryoreduction/annealing studies. Biochemistry. 54:7089–7097.
  • Di Blasio AM, Voutilainen R, Jaffe RB, Miller WL. 1987. Hormonal regulation of messenger ribonucleic acids for P450scc (cholesterol side-chain cleavage enzyme) and P450c17 (17α-hydroxylase/17,20-lyase) in cultured human fetal adrenal cells. J Clin Endocrinol Metab. 65:170–175.
  • Ding L, Murphy MB, He Y, Xu Y, Yeung LW, Wang J, Zhou B, Lam PK, Wu RS, Giesy JP. 2007. Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line. Environ Toxicol Chem. 26:764–772.
  • Dowie LJ, Smith JE, MacGilchrist AJ, Fraser R, Honour JW, Reid JL, Kenyon CJ. 1988. In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis. Eur J Clin Pharmacol. 35:625–629.
  • Drewett JG, Adams-Hays RL, Ho BY, Hegge DJ. 2002. Nitric oxide potently inhibits the rate-limiting enzymatic step in steroidogenesis. Mol Cell Endocrinol. 194:39–50.
  • Fassnacht M, Hahner S, Beuschlein F, Klink A, Reincke M, Allolio B. 2000. New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line. Eur J Clin Invest. 30 (Suppl 3):76–82.
  • Garcia MM, Acquier A, Suarez G, Gomez NV, Gorostizaga A, Mendez CF, Paz C. 2012. Cisplatin inhibits testosterone synthesis by a mechanism that includes the action of reactive oxygen species (ROS) at the level of P450scc. Chem Biol Interact. 199:185–191.
  • Ghayee HK, Auchus RJ. 2007. Basic concepts and recent developments in human steroid hormone biosynthesis. Rev Endocr Metabol Disorders. 8:289–300.
  • Gregoraszczuk EL, Ptak A, Karpeta A, Fiedor E, Wrobel A, Milewicz T, Falandysz J. 2014. Hexachlorobenzene and pentachlorobenzene accumulation, metabolism and effect on steroid secretion and on CYP11A1 and CYP19 expression in cultured human placental tissue. Reprod Toxicol. 43:102–110.
  • Guo IC, Hu MC, Chung BC. 2003. Transcriptional regulation of CYP11A1. J Biomed Sci. 10:593–598.
  • Guo IC, Shih MC, Lan HC, Hsu NC, Hu MC, Chung BC. 2007. Transcriptional regulation of human CYP11A1 in gonads and adrenals. J Biomed Sci. 14:509–515.
  • Guryev O, Carvalho RA, Usanov S, Gilep A, Estabrook RW. 2003. A pathway for the metabolism of vitamin D3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc Natl Acad Sci USA. 100:14754–14759.
  • Hartmann RW, Muller U, Ehmer PB. 2003. Discovery of selective CYP11B2 (aldosterone synthase) inhibitors for the therapy of congestive heart failure and myocardial fibrosis. Eur J Med Chem. 38:363–366.
  • Huang BM, Hsiao KY, Chuang PC, Wu MH, Pan HA, Tsai SJ. 2004. Upregulation of steroidogenic enzymes and ovarian 17β-estradiol in human granulosa-lutein cells by Cordyceps sinensis mycelium. Biol Reprod. 70:1358–1364.
  • Johansson MK, Sanderson JT, Lund BO. 2002. Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 16:113–121.
  • Kau MM, Kan SF, Wang JR, Wang PS. 2005. Inhibitory effects of digoxin and ouabain on aldosterone synthesis in human adrenocortical NCI-H295 cells. J Cell Physiol. 205:393–401.
  • Kisselev P, Tuckey RC, Woods ST, Triantopoulos T, Schwarz D. 1999. Enzymatic properties of vesicle-reconstituted human cytochrome P450SCC (CYP11A1) differences in functioning of the mitochondrial electron-transfer chain using human and bovine adrenodoxin and activation by cardiolipin. Eur J Biochem. 260:768–773.
  • Kraugerud M, Zimmer KE, Ropstad E, Verhaegen S. 2011. Perfluorinated compounds differentially affect steroidogenesis and viability in the human adrenocortical carcinoma (H295R) in vitro cell assay. Toxicol Lett. 205:62–68.
  • Lambeth JD. 1983. 22-Ketocholesterol: A potent competitive inhibitor of cytochrome P-450scc-dependent side-chain cleavage of cholesterol. Mol Pharmacol. 23:743–747.
  • Lan HC, Lin IW, Yang ZJ, Lin JH. 2015. Low-dose bisphenol a activates Cyp11a1 Gene expression and corticosterone secretion in adrenal gland via the JNK signaling pathway. Toxicol Sci. 148:26–34.
  • Lin CW, Chang YH, Pu HF. 2012. Mitotane exhibits dual effects on steroidogenic enzymes gene transcription under basal and cAMP-stimulating microenvironments in NCI-H295 cells. Toxicology. 298:14–23.
  • Mast N, Annalora AJ, Lodowski DT, Palczewski K, Stout CD, Pikuleva IA. 2011. Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme CYP11A1. J Biol Chem. 286:5607–5613.
  • Mast N, Linger M, Pikuleva IA. 2013. Inhibition and stimulation of activity of purified recombinant CYP11A1 by therapeutic agents. Mol Cell Endocrinol. 371:100–106.
  • Mauger JW. 1989. The impact of innovative drug delivery systems on drug toxicity. J Clin Toxicol. 27:v–vii.
  • McQuarters AB, Wolf MW, Hunt AP, Lehnert N. 2014. 1958-2014: after 56 years of research, cytochrome P450 reactivity is finally explained. Angew Chem Int Ed. 53:4750–4752.
  • Mesiano S, Katz SL, Lee JY, Jaffe RB. 1997. Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen regulation. J Clin Endocrinol Metab. 82:1390–1396.
  • Milczarek R, Sokolowska E, Rybakowska I, Kaletha K, Klimek J. 2016. Paraquat inhibits progesterone synthesis in human placental mitochondria. Placenta. 43:41–46.
  • Mosa A, Neunzig J, Gerber A, Zapp J, Hannemann F, Pilak P, Bernhardt R. 2015. 2β- and 16β-Hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation. J Steroid Biochem Mol Biol. 150:1–10.
  • Nelson-DeGrave VL, Wickenheisser JK, Cockrell JE, Wood JR, Legro RS, Strauss JF, 3rd, McAllister JM. 2004. Valproate potentiates androgen biosynthesis in human ovarian theca cells. Endocrinology. 145:799–808.
  • Ortiz de Montellano PR. 2015. Substrate oxidation. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 111–176.
  • Oskarsson A, Ohlsson Andersson A. 2016. Suppressed sex hormone biosynthesis by alkylresorcinols: a possible link to chemoprevention. Nutr Cancer. 68:978–987.
  • Pagotto MA, Roldan ML, Pagotto RM, Lugano MC, Pisani GB, Rogic G, Molinas SM, Trumper L, Pignataro OP, Monasterolo LA. 2011. Localization and functional activity of cytochrome P450 side chain cleavage enzyme (CYP11A1) in the adult rat kidney. Mol Cell Endocrinol. 332:253–260.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Picado-Leonard J, Voutilainen R, Kao LC, Chung BC, Strauss JF, 3rd, Miller WL. 1988. Human adrenodoxin: cloning of three cDNAs and cycloheximide enhancement in JEG-3 cells. J Biol Chem. 263:3240–3244.
  • Sawetawan C, Carr BR, McGee E, Bird IM, Hong TL, Rainey WE. 1996. Inhibin and activin differentially regulate androgen production and 17α-hydroxylase expression in human ovarian thecal-like tumor cells. J Endocrinol. 148:213–221.
  • Schiffer L, Brixius-Anderko S, Hannemann F, Zapp J, Neunzig J, Thevis M, Bernhardt R. 2016. Metabolism of oral turinabol by human steroid hormone-synthesizing cytochrome P450 enzymes. Drug Metab Dispos. 44:227–237.
  • Schuster I, Bernhardt R. 2007. Inhibition of cytochromes P450: existing and new promising therapeutic targets. Drug Metab Rev. 39:481–499.
  • Seissler J, Schott M, Steinbrenner H, Peterson P, Scherbaum WA. 1999. Autoantibodies to adrenal cytochrome P450 antigens in isolated Addison's disease and autoimmune polyendocrine syndrome type II. Exp Clinical Endocrinol Diabetes. 107:208–213.
  • Shih MC, Chiu YN, Hu MC, Guo IC, Chung BC. 2011. Regulation of steroid production: analysis of Cyp11a1 promoter. Mol Cell Endocrinol. 336:80–84.
  • Slominski A, Semak I, Wortsman J, Zjawiony J, Li W, Zbytek B, Tuckey RC. 2006. An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2. FEBS J. 273:2891–2901.
  • Slominski AT, Kim TK, Li W, Yi AK, Postlethwaite A, Tuckey RC. 2014. The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions. J Steroid Biochem Mol Biol. 144:28–39.
  • Slominski AT, Li W, Kim T-K, Semak I, Wang J, Zjawiony JK, Tuckey RC. 2015. Novel activities of CYP11A1 and their potential physiological significance. J Steroid Biochem Mol Biol. 151:25–37.
  • Song R, He Y, Murphy MB, Yeung LW, Yu RM, Lam MH, Lam PK, Hecker M, Giesy JP, Wu RS, et al. 2008. Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line. Chemosphere. 71:1888–1894.
  • Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW. 2011. Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci USA. 108:10139–10143.
  • Tang EKY, Chen JJ, Janjetovic Z, Tieu EW, Slominski AT, Li W, Tuckey RC. 2013. Hydroxylation of CYP11A1-derived products of vitamin D3 metabolism by human and mouse CYP27B1. Drug Metab Dispos. 41:1112-1124.
  • Tuckey RC, Cameron KJ. 1993a. Catalytic properties of cytochrome P-450scc purified from the human placenta: comparison to bovine cytochrome P-450scc. Biochim Biophys Acta. 1163:185–194.
  • Tuckey RC, Cameron KJ. 1993b. Side-chain specificities of human and bovine cytochromes P-450scc. Eur J Biochem. 217:209–215.
  • Tuckey RC, Janjetovic Z, Li W, Nguyen MN, Zmijewski MA, Zjawiony J, Slominski A. 2008. Metabolism of 1α-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1α,20-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 112:213–219.
  • Tuckey RC, Li W, Shehabi HZ, Janjetovic Z, Nguyen MN, Kim TK, Chen J, Howell DE, Benson HA, Sweatman T, et al. 2011. Production of 22-hydroxy metabolites of vitamin D3 by cytochrome P450scc (CYP11A1) and analysis of their biological activities on skin cells. Drug Metab Dispos. 39:1577–1588.
  • Tuckey RC, Li W, Zjawiony JK, Zmijewski MA, Nguyen MN, Sweatman T, Miller D, Slominski A. 2008. Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc. FEBS J. 275:2585–2596.
  • Tuckey RC, Nguyen MN, Slominski A. 2008. Kinetics of vitamin D3 metabolism by cytochrome P450scc (CYP11A1) in phospholipid vesicles and cyclodextrin. Int J Biochem Cell Biol. 40:2619–2626.
  • Tuckey RC, Slominski AT, Cheng CY, Chen J, Kim TK, Xiao M, Li W. 2014. Lumisterol is metabolized by CYP11A1: discovery of a new pathway. Int J Biochem Cell Biol. 55:24–34.
  • van Koetsveld PM, Vitale G, Feelders RA, Waaijers M, Sprij-Mooij DM, de Krijger RR, Speel EJ, Hofland J, Lamberts SW, de Herder WW, et al. 2013. Interferon-β is a potent inhibitor of cell growth and cortisol production in vitro and sensitizes human adrenocortical carcinoma cells to mitotane. Endocr Relat Cancer. 20:443–454.
  • van Lier JE, Mast N, Pikuleva IA. 2015. Cholesterol hydroperoxides as substrates for cholesterol-metabolizing cytochrome P450 enzymes and alternative sources of 25-hydroxycholesterol and other oxysterols. Angew Chem Int Ed. 54:11138–11142.
  • Wu CC, Mei S, Cheng J, Ding Y, Weidenhammer A, Garcia V, Zhang F, Gotlinger K, Manthati VL, Falck JR, et al. 2013. Androgen-sensitive hypertension associates with upregulated vascular CYP4A12-20-HETE synthase. J Am Soc Nephrol. 24:1288–1296.
  • Ye L, Su ZJ, Ge RS. 2011. Inhibitors of testosterone biosynthetic and metabolic activation enzymes. Molecules. 16:9983–10001.
  • Yoshimoto FK, Jung IJ, Goyal S, Gonzalez E, Guengerich FP. 2016. Isotope-labeling studies support the electrophilic Compound I iron active species, FeO3+, for the carbon-carbon bond cleavage reaction of the cholesterol side-chain cleavage enzyme, cytochrome P450 11A1. J Am Chem Soc. 138:12124–12141.
  • Zhang D, Flint O, Wang L, Gupta A, Westhouse RA, Zhao W, Raghavan N, Caceres-Cortes J, Marathe P, Shen G, et al. 2012. Cytochrome P450 11A1 bioactivation of a kinase inhibitor in rats: use of radioprofiling, modulation of metabolism, and adrenocortical cell lines to evaluate adrenal toxicity. Chem Res Toxicol. 25:556–571.

References

  • Asp V, Ulleras E, Lindstrom V, Bergstrom U, Oskarsson A, Brandt I. 2010. Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells. Toxicol Appl Pharmacol. 242:281–289.
  • Ayub M, Levell MJ. 1989. Inhibition of human adrenal steroidogenic enzymes in vitro by imidazole drugs including ketoconazole. J Steroid Biochem. 32:515–524.
  • Barugh AJ, Gray P, Shenkin SD, MacLullich AM, Mead GE. 2014. Cortisol levels and the severity and outcomes of acute stroke: a systematic review. J Neurol. 261:533–545.
  • Bernhardt R. 2016. The potential of targeting CYP11B. Exp Opin Ther Targets. 20:923–934.
  • Bureik M, Hubel K, Dragan CA, Scher J, Becker H, Lenz N, Bernhardt R. 2004. Development of test systems for the discovery of selective human aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1) inhibitors. Discovery of a new lead compound for the therapy of congestive heart failure, myocardial fibrosis and hypertension. Mol Cell Endocrinol. 217:249–254.
  • Bureik M, Lisurek M, Bernhardt R. 2002. The human steroid hydroxylases CYP11B1 and CYP11B2. Biol Chem. 383:1537–1551.
  • Bureik M, Zeeh A, Bernhardt R. 2002. Modulation of steroid hydroxylase activity in stably transfected V79MZh11B1 and V79MZh11B2 cells by PKC and PKD inhibitors. Endocr Res. 28:351–355.
  • Cheng SC, Suzuki K, Sadee W, Harding BW. 1976. Effects of spironolactone, canrenone and canrenoate-K on cytochrome P450, and 11β- and 18-hydroxylation in bovine and human adrenal cortical mitochondria. Endocrinology. 99:1097–1106.
  • Chiodini I, Adda G, Scillitani A, Coletti F, Morelli V, Di Lembo S, Epaminonda P, Masserini B, Beck-Peccoz P, Orsi E, et al. 2007. Cortisol secretion in patients with type 2 diabetes: Relationship with chronic complications. Diabetes Care. 30:83–88.
  • Connolly CK, Wills MR. 1967. Plasma cortisol levels in heart failure. Brit Med J. 2:25–27.
  • Coulter CL, Jaffe RB. 1998. Functional maturation of the primate fetal adrenal in vivo: 3. Specific zonal localization and developmental regulation of CYP21A2 (P450c21) and CYP11B1/CYP11B2 (P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis. Endocrinology. 139:5144–5150.
  • Denner K, Rainey WE, Pezzi V, Bird IM, Bernhardt R, Mathis JM. 1996. Differential regulation of 11β-hydroxylase and aldosterone synthase in human adrenocortical H295R cells. Mol Cell Endocrinol. 121:87–91.
  • Denner K, Vogel R, Schmalix W, Doehmer J, Bernhardt R. 1995. Cloning and stable expression of the human mitochondrial cytochrome P45011B1 cDNA in V79 Chinese hamster cells and their application for testing of potential inhibitors. Pharmacogenetics. 5:89–96.
  • Ding L, Murphy MB, He Y, Xu Y, Yeung LW, Wang J, Zhou B, Lam PK, Wu RS, Giesy JP. 2007. Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line. Environ Toxicol Chem. 26:764–772.
  • Domalik LJ, Chaplin DD, Kirkman MS, Wu RC, Liu WW, Howard TA, Seldin MF, Parker KL. 1991. Different isozymes of mouse 11β-hydroxylase produce mineralocorticoids and glucocorticoids. Mol Endocrinol. 5:1853–1861.
  • Ehmer PB, Bureik M, Bernhardt R, Muller U, Hartmann RW. 2002. Development of a test system for inhibitors of human aldosterone synthase (CYP11B2): screening in fission yeast and evaluation of selectivity in V79 cells. J Steroid Biochem Mol Biol. 81:173–179.
  • Emmerich J, van Koppen CJ, Burkhart JL, Engeli RT, Hu Q, Odermatt A, Hartmann RW. 2018. Accelerated skin wound healing by selective 11β-hydroxylase (CYP11B1) inhibitors. Eur J Med Chem. 143:591–597.
  • Emmerich J, van Koppen CJ, Burkhart JL, Hu Q, Siebenburger L, Boerger C, Scheuer C, Laschke MW, Menger MD, Hartmann RW. 2017. Lead optimization generates CYP11B1 inhibitors of pyridylmethyl isoxazole type with improved pharmacological profile for the treatment of Cushing's disease. J Med Chem. 60:5086–5098.
  • Engelhardt D, Weber MM. 1994. Therapy of Cushing's syndrome with steroid biosynthesis inhibitors. J Steroid Biochem Mol Biol. 49:261–267.
  • Fassnacht M, Hahner S, Beuschlein F, Klink A, Reincke M, Allolio B. 2000. New mechanisms of adrenostatic compounds in a human adrenocortical cancer cell line. Eur J Clin Invest. 30 (Suppl 3):76–82.
  • Fisher A, Friel EC, Bernhardt R, Gomez-Sanchez C, Connell JM, Fraser R, Davies E. 2001. Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11β-hydroxylase. J Clin Endocrinol Metab. 86:4326–4329.
  • Gobbi S, Hu Q, Zimmer C, Belluti F, Rampa A, Hartmann RW, Bisi A. 2016. Targeting steroidogenic cytochromes P450 (CYPs) with 6-substituted 1-imidazolylmethylxanthones. ChemMedChem. 11:1770–1777.
  • Gobbi S, Hu Q, Zimmer C, Belluti F, Rampa A, Hartmann RW, Bisi A. 2017. Drifting of heme-coordinating group in imidazolylmethylxanthones leading to improved selective inhibition of CYP11B1. Eur J Med Chem. 139:60–67.
  • Grombein CM, Hu Q, Heim R, Rau S, Zimmer C, Hartmann RW. 2015. 1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors. Eur J Med Chem. 89:597–605.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Hahner S, Stuermer A, Kreissl M, Reiners C, Fassnacht M, Haenscheid H, Beuschlein F, Zink M, Lang K, Allolio B, et al. 2008. [123I]-Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes. J Clin Endocrinol Metab. 93:2358–2365.
  • Hartmann RW, Muller U, Ehmer PB. 2003. Discovery of selective CYP11B2 (aldosterone synthase) inhibitors for the therapy of congestive heart failure and myocardial fibrosis. Eur J Med Chem. 38:363–366.
  • Hu Q, Yin L, Ali A, Cooke AJ, Bennett J, Ratcliffe P, Lo MM, Metzger E, Hoyt S, Hartmann RW. 2015. Novel pyridyl substituted 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines as potent and selective aldosterone synthase inhibitors with improved in vitro metabolic stability. J Med Chem. 58:2530–2537.
  • Hu Q, Yin L, Jagusch C, Hille UE, Hartmann RW. 2010. Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors. J Med Chem. 53:5049–5053.
  • Johansson M, Larsson C, Bergman A, Lund BO. 1998. Structure-activity relationship for inhibition of CYP11B1-dependent glucocorticoid synthesis in Y1 cells by aryl methyl sulfones. Pharmacol Toxicol. 83:225–230.
  • Johansson MK, Sanderson JT, Lund BO. 2002. Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 16:113–121.
  • Kau MM, Kan SF, Wang JR, Wang PS. 2005. Inhibitory effects of digoxin and ouabain on aldosterone synthesis in human adrenocortical NCI-H295 cells. J Cell Physiol. 205:393–401.
  • Kau MM, Wang JR, Tsai SC, Yu CH, Wang PS. 2012. Inhibitory effect of bufalin and cinobufagin on steroidogenesis via the activation of ERK in human adrenocortical cells. Brit J Pharmacol. 165:1868–1876.
  • Kenyon CJ, Fraser R, Birnie GG, Connell JM, Lever AF. 1986. Dose related in vitro effects of ranitidine and cimetidine on basal and ACTH-stimulated steroidogenesis. Gut. 27:1143–1146.
  • Kim B, Moon JY, Choi MH, Yang HH, Lee S, Lim KS, Yoon SH, Yu KS, Jang IJ, Cho JY. 2013. Global metabolomics and targeted steroid profiling reveal that rifampin, a strong human PXR activator, alters endogenous urinary steroid markers. J Proteome Res. 12:1359–1368.
  • Lin CW, Chang YH, Pu HF. 2012. Mitotane exhibits dual effects on steroidogenic enzymes gene transcription under basal and cAMP-stimulating microenvironments in NCI-H295 cells. Toxicology. 298:14–23.
  • Lin TC, Chien SC, Hsu PC, Li LA. 2006. Mechanistic study of polychlorinated biphenyl 126-induced CYP11B1 and CYP11B2 up-regulation. Endocrinology. 147:1536–1544.
  • Mitrunen K, Jourenkova N, Kataja V, Eskelinen M, Kosma VM, Benhamou S, Vainio H, Uusitupa M, Hirvonen A. 2000. Steroid metabolism gene CYP17 polymorphism and the development of breast cancer. Cancer Epidemiol Biomarkers Prev. 9:1343–1348.
  • Muller-Vieira U, Angotti M, Hartmann RW. 2005. The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11β-hydroxylase) inhibitors. J Steroid Biochem Mol Biol. 96:259–270.
  • Nonaka Y, Okamoto M. 1991. Functional expression of the cDNAs encoding rat 11β-hydroxylase [cytochrome P450(11β)] and aldosterone synthase [cytochrome P450(11β, aldo)]. Eur J Biochem. 202:897–902.
  • Okahara K, Sun B, Kambayashi J. 1998. Upregulation of prostacyclin synthesis-related gene expression by shear stress in vascular endothelial cells. Arterioscler Thromb Vasc Biol. 18:1922–1926.
  • Otton SV, Schadel M, Cheung SW, Kaplan HL, Busto UE, Sellers EM. 1993. CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Clin Pharmacol Ther. 54:463–472.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Papillon JP, Adams CM, Hu QY, Lou C, Singh AK, Zhang C, Carvalho J, Rajan S, Amaral A, Beil ME, et al. 2015. Structure-activity relationships, pharmacokinetics, and in vivo activity of CYP11B2 and CYP11B1 inhibitors. J Med Chem. 58:4749–4770.
  • Parr MK, Zöllner A, Fussholler G, Opfermann G, Schlörer N, Zorio M, Bureik M, Schanzer W. 2012. Unexpected contribution of cytochrome P450 enzymes CYP11B2 and CYP21, as well as CYP3A4 in xenobiotic androgen elimination–insights from metandienone metabolism. Toxicol Lett. 213:381–391.
  • Pinto-Bazurco Mendieta MA, Negri M, Jagusch C, Muller-Vieira U, Lauterbach T, Hartmann RW. 2008. Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer. J Med Chem. 51:5009–5018.
  • Roumen L, Sanders MP, Pieterse K, Hilbers PA, Plate R, Custers E, de Gooyer M, Smits JF, Beugels I, Emmen J, et al. 2007. Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics. J Comput Aided Mol Des. 21:455–471.
  • Schiffer L, Brixius-Anderko S, Hannemann F, Zapp J, Neunzig J, Thevis M, Bernhardt R. 2016. Metabolism of oral turinabol by human steroid hormone-synthesizing cytochrome P450 enzymes. Drug Metab Dispos. 44:227–237.
  • Schiffer L, Müller AR, Hobler A, Brixius-Anderko S, Zapp J, Hannemann F, Bernhardt R. 2016. Biotransformation of the mineralocorticoid receptor antagonists spironolactone and canrenone by human CYP11B1 and CYP11B2: characterization of the products and their influence on mineralocorticoid receptor transactivation. J Steroid Biochem Mol Biol. 163:68–76.
  • Schroeder RL, Tram P, Liu J, Foroozesh M, Sridhar J. 2016. Novel functionalized 5-(phenoxymethyl)-1,3-dioxane analogs exhibiting cytochrome P450 inhibition: a patent evaluation WO2015048311 (A1). Exp Opin Ther Pat. 26:139–147.
  • Ulmschneider S, Muller-Vieira U, Mitrenga M, Hartmann RW, Oberwinkler-Marchais S, Klein CD, Bureik M, Bernhardt R, Antes I, Lengauer T. 2005. Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: potent inhibitors of aldosterone synthase. J Med Chem. 48:1796–1805.
  • van Koetsveld PM, Vitale G, Feelders RA, Waaijers M, Sprij-Mooij DM, de Krijger RR, Speel EJ, Hofland J, Lamberts SW, de Herder WW, et al. 2013. Interferon-β is a potent inhibitor of cell growth and cortisol production in vitro and sensitizes human adrenocortical carcinoma cells to mitotane. Endocrine Relat Cancer. 20:443–454.
  • Vermeulen A, Paridaens R, Heuson JC. 1983. Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocrinol. 19:673–682.
  • Voets M, Antes I, Scherer C, Muller-Vieira U, Biemel K, Barassin C, Marchais-Oberwinkler S, Hartmann RW. 2005. Heteroaryl-substituted naphthalenes and structurally modified derivatives: Selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis. J Med Chem. 48:6632–6642.
  • Voets M, Antes I, Scherer C, Muller-Vieira U, Biemel K, Marchais-Oberwinkler S, Hartmann RW. 2006. Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. J Med Chem. 49:2222–2231.
  • Vukelic S, Stojadinovic O, Pastar I, Rabach M, Krzyzanowska A, Lebrun E, Davis SC, Resnik S, Brem H, Tomic-Canic M. 2011. Cortisol synthesis in epidermis is induced by IL-1 and tissue injury. J Biol Chem. 286:10265–10275.
  • Walker BR. 2006. Cortisol–cause and cure for metabolic syndrome? Diabetic Med. 23:1281–1288.
  • Yin LN, Lucas S, Maurer F, Kazmaier U, Hu QZ, Hartmann RW. 2012. Novel imidazol-1-ylmethyl substituted 1,2,5,6-tetrahydropyrrolo-3,2,1-ij-quinolin-4-ones as potent and selective CYP11B1 inhibitors for the treatment of Cushing's syndrome. J Med Chem. 55:6629–6633.
  • Zhu W, Hu Q, Hanke N, van Koppen CJ, Hartmann RW. 2014. Potent 11β-hydroxylase inhibitors with inverse metabolic stability in human plasma and hepatic S9 fractions to promote wound healing. J Med Chem. 57:7811–7817.

References

  • Amar L, Azizi M, Menard J, Peyrard S, Watson C, Plouin PF. 2010. Aldosterone synthase inhibition with LCI699: a proof-of-concept study in patients with primary aldosteronism. Hypertension. 56:831–838.
  • Asp V, Ulleras E, Lindstrom V, Bergstrom U, Oskarsson A, Brandt I. 2010. Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells. Toxicol Appl Pharmacol. 242:281–289.
  • Azizi M, Amar L, Menard J. 2013. Aldosterone synthase inhibition in humans. Nephrol Dialysis Transplant. 28:36–43.
  • Bernhardt R. 2016. The potential of targeting CYP11B. Exp Opin Ther Targets. 20:923–934.
  • Blaha L, Hilscherova K, Mazurova E, Hecker M, Jones PD, Newsted JL, Bradley PW, Gracia T, Duris Z, Horka I, et al. 2006. Alteration of steroidogenesis in H295R cells by organic sediment contaminants and relationships to other endocrine disrupting effects. Environ Int. 32:749–757.
  • Bogman K, Schwab D, Delporte ML, Palermo G, Amrein K, Mohr S, De Vera Mudry MC, Brown MJ, Ferber P. 2017. Preclinical and early clinical profile of a highly selective and potent oral inhibitor of aldosterone synthase (CYP11B2). Hypertension. 69:189–196.
  • Brown NJ. 2005. Aldosterone and end-organ damage. Curr Opin Nephrol Hypertens. 14:235–241.
  • Brunssen C, Hofmann A, Peitzsch M, Frenzel A, Ziegler CG, Brown NF, Weldon SM, Eisenhofer G, Willenberg HS, Bornstein SR, et al. 2017. Impact of aldosterone synthase inhibitor FAD286 on steroid hormone profile in human adrenocortical cells. Hormone Metab Res. 49:701–706.
  • Bureik M, Hubel K, Dragan CA, Scher J, Becker H, Lenz N, Bernhardt R. 2004. Development of test systems for the discovery of selective human aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1) inhibitors. Discovery of a new lead compound for the therapy of congestive heart failure, myocardial fibrosis and hypertension. Mol Cell Endocrinol. 217:249–254.
  • Bureik M, Mion A, Kenyon CJ, Bernhardt R. 2005. Inhibition of aldosterone biosynthesis by staurosporine. Biol Chem. 386:663–669.
  • Bureik M, Zeeh A, Bernhardt R. 2002. Modulation of steroid hydroxylase activity in stably transfected V79MZh11B1 and V79MZh11B2 cells by PKC and PKD inhibitors. Endocr Res. 28:351–355.
  • Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, et al. 2008. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension. 51:1403–1419.
  • Cohn JN, Colucci W. 2006. Cardiovascular effects of aldosterone and post-acute myocardial infarction pathophysiology. Am J Cardiol. 97:4f–12f.
  • Condon JC, Pezzi V, Drummond BM, Yin S, Rainey WE. 2002. Calmodulin-dependent kinase I regulates adrenal cell expression of aldosterone synthase. Endocrinology. 143:3651–3657.
  • Coulter CL, Jaffe RB. 1998. Functional maturation of the primate fetal adrenal in vivo: 3. Specific zonal localization and developmental regulation of CYP21A2 (P450c21) and CYP11B1/CYP11B2 (P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis. Endocrinology. 139:5144–5150.
  • Denner K, Rainey WE, Pezzi V, Bird IM, Bernhardt R, Mathis JM. 1996. Differential regulation of 11β-hydroxylase and aldosterone synthase in human adrenocortical H295R cells. Mol Cell Endocrinol. 121:87–91.
  • Ding L, Murphy MB, He Y, Xu Y, Yeung LW, Wang J, Zhou B, Lam PK, Wu RS, Giesy JP. 2007. Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line. Environ Toxicol Chem. 26:764–772.
  • Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC. 2011. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 124:1046–1058.
  • Ehmer PB, Bureik M, Bernhardt R, Muller U, Hartmann RW. 2002. Development of a test system for inhibitors of human aldosterone synthase (CYP11B2): screening in fission yeast and evaluation of selectivity in V79 cells. J Steroid Biochem Mol Biol. 81:173–179.
  • Funder JW, Mihailidou AS. 2009. Aldosterone and mineralocorticoid receptors: clinical studies and basic biology. Mol Cell Endocrinol. 301:2–6.
  • Gennari-Moser C, Khankin EV, Escher G, Burkhard F, Frey BM, Karumanchi SA, Frey FJ, Mohaupt MG. 2013. Vascular endothelial growth factor-A and aldosterone: relevance to normal pregnancy and preeclampsia. Hypertension. 61:1111–1117.
  • Gobbi S, Hu Q, Zimmer C, Belluti F, Rampa A, Hartmann RW, Bisi A. 2016. Targeting steroidogenic cytochromes P450 (CYPs) with 6-substituted 1-imidazolylmethylxanthones. ChemMedChem. 11:1770–1777.
  • Grombein CM, Hu Q, Heim R, Rau S, Zimmer C, Hartmann RW. 2015. 1-Phenylsulfinyl-3-(pyridin-3-yl)naphthalen-2-ols: a new class of potent and selective aldosterone synthase inhibitors. Eur J Med Chem. 89:597–605.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Hahner S, Stuermer A, Kreissl M, Reiners C, Fassnacht M, Haenscheid H, Beuschlein F, Zink M, Lang K, Allolio B, et al. 2008. [123I]-Iodometomidate for molecular imaging of adrenocortical cytochrome P450 family 11B enzymes. J Clin Endocrinol Metab. 93:2358–2365.
  • Hakki T, Hubel K, Waldmann H, Bernhardt R. 2011. The development of a whole-cell based medium throughput screening system for the discovery of human aldosterone synthase (CYP11B2) inhibitors: old drugs disclose new applications for the therapy of congestive heart failure, myocardial fibrosis and hypertension. J Steroid Biochem Mol Biol. 125:120–128.
  • Hartmann RW, Muller U, Ehmer PB. 2003. Discovery of selective CYP11B2 (aldosterone synthase) inhibitors for the therapy of congestive heart failure and myocardial fibrosis. Eur J Med Chem. 38:363–366.
  • Hoyt SB, Taylor J, London C, Ali A, Ujjainwalla F, Tata J, Struthers M, Cully D, Wisniewski T, Ren N, et al. 2017. Discovery of indazole aldosterone synthase (CYP11B2) inhibitors as potential treatments for hypertension. Bioorg Med Chem Lett. 27:2384–2388.
  • Hu Q, Jagusch C, Hille UE, Haupenthal J, Hartmann RW. 2010. Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer. J Med Chem. 53:5749–5758.
  • Hu Q, Yin L, Ali A, Cooke AJ, Bennett J, Ratcliffe P, Lo MM, Metzger E, Hoyt S, Hartmann RW. 2015. Novel pyridyl substituted 4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines as potent and selective aldosterone synthase inhibitors with improved in vitro metabolic stability. J Med Chem. 58:2530–2537.
  • Karns AD, Bral JM, Hartman D, Peppard T, Schumacher C. 2013. Study of aldosterone synthase inhibition as an add-on therapy in resistant hypertension. J Clin Hypertens. 15:186–192.
  • Kau MM, Kan SF, Wang JR, Wang PS. 2005. Inhibitory effects of digoxin and ouabain on aldosterone synthesis in human adrenocortical NCI-H295 cells. J Cell Physiol. 205:393–401.
  • Kau MM, Wang JR, Tsai SC, Yu CH, Wang PS. 2012. Inhibitory effect of bufalin and cinobufagin on steroidogenesis via the activation of ERK in human adrenocortical cells. Brit J Pharmacol. 165:1868–1876.
  • Keshava C, Whipkey D, Weston A. 2005. Transcriptional signatures of environmentally relevant exposures in normal human mammary epithelial cells: Benzo[a]pyrene. Cancer Lett. 221:201–211.
  • Kim B, Moon JY, Choi MH, Yang HH, Lee S, Lim KS, Yoon SH, Yu KS, Jang IJ, Cho JY. 2013. Global metabolomics and targeted steroid profiling reveal that rifampin, a strong human PXR activator, alters endogenous urinary steroid markers. J Proteome Res. 12:1359–1368.
  • Kobuke K, Oki K, Gomez-Sanchez CE, Gomez-Sanchez EP, Ohno H, Itcho K, Yoshii Y, Yoneda M, Hattori N. 2018. Calneuron 1 increased Ca2+ in the endoplasmic reticulum and aldosterone production in aldosterone-producing adenoma. Hypertension. 71:125–133.
  • LeHoux JG, Dupuis G, Lefebvre A. 2001. Control of CYP11B2 gene expression through differential regulation of its promoter by atypical and conventional protein kinase C isoforms. J Biol Chem. 276:8021–8028.
  • LeHoux JG, Lefebvre A. 2004. On the control of the hCYP11B2 gene expressing cytochrome P450 aldosterone synthase. Endocr Res. 30:807–812.
  • Lin TC, Chien SC, Hsu PC, Li LA. 2006. Mechanistic study of polychlorinated biphenyl 126-induced CYP11B1 and CYP11B2 up-regulation. Endocrinology. 147:1536–1544.
  • Lucas S, Heim R, Negri M, Antes I, Ries C, Schewe KE, Bisi A, Gobbi S, Hartmann RW. 2008. Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach. J Med Chem. 51:6138–6149.
  • Lucas S, Heim R, Ries C, Schewe KE, Birk B, Hartmann RW. 2008. In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives. J Med Chem. 51:8077–8087.
  • Martin RE, Aebi JD, Hornsperger B, Krebs H-J, Kuhn B, Kuglstatter A, Alker AM, Märki HP, Müller S, Burger D et al. 2015. Discovery of 4-aryl-5,6,7,8-tetrahydroisoquinolines as potent, selective, and orally active aldosterone synthase (CYP11B2) inhibitors: in vivo evaluation in rodents and cynomolgus monkeys. J Med Chem. 58:8054-8065.
  • Matsuda K, Uruno A, Kogure N, Sugawara K, Shimada H, Nezu M, Saito-Ito T, Iki Y, Kudo M, Shimizu K, et al. 2014. Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells. Mol Cell Endocrinol. 383:60–68.
  • Meguro M, Miyauchi S, Kanao Y, Naito S, Suzuki K, Inoue S, Yamada K, Homma T, Chiba K, Nara F, et al. 2017. 4-Anilino-pyrimidine, novel aldosterone synthase (CYP11B2) inhibitors bearing pyrimidine structures. Bioorg Med Chem Lett. 27:1902–1906.
  • Moore TD, Nawarskas JJ, Anderson JR. 2003. Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure. Heart Disease. 5:354–363.
  • Muller-Vieira U, Angotti M, Hartmann RW. 2005. The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11β-hydroxylase) inhibitors. J Steroid Biochem Mol Biol. 96:259–270.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Papillon JP, Adams CM, Hu QY, Lou C, Singh AK, Zhang C, Carvalho J, Rajan S, Amaral A, Beil ME, et al. 2015. Structure-activity relationships, pharmacokinetics, and in vivo activity of CYP11B2 and CYP11B1 inhibitors. J Med Chem. 58:4749–4770.
  • Parr MK, Zöllner A, Fussholler G, Opfermann G, Schlörer N, Zorio M, Bureik M, Schanzer W. 2012. Unexpected contribution of cytochrome P450 enzymes CYP11B2 and CYP21, as well as CYP3A4 in xenobiotic androgen elimination–insights from metandienone metabolism. Toxicol Lett. 213:381–391.
  • Pimenta E, Calhoun DA. 2006. Aldosterone, dietary salt, and renal disease. Hypertension. 48:209–210.
  • Pinto-Bazurco Mendieta MA, Negri M, Jagusch C, Muller-Vieira U, Lauterbach T, Hartmann RW. 2008. Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer. J Med Chem. 51:5009–5018.
  • Roumen L, Sanders MP, Pieterse K, Hilbers PA, Plate R, Custers E, de Gooyer M, Smits JF, Beugels I, Emmen J, et al. 2007. Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics. J Comput Aided Mol Des. 21:455–471.
  • Roumen L, Van Hoof B, Pieterse K, Hilbers PA, Custers EM, Plate R, De Gooyer M, Beugels IP, Emmen JM, Leysen D, et al. 2011. Application of a ligand-based theoretical approach to derive conversion paths and ligand conformations in CYP11B2-mediated aldosterone formation. J Computat Chem. 32:2441–2448.
  • Schiffer L, Brixius-Anderko S, Hannemann F, Zapp J, Neunzig J, Thevis M, Bernhardt R. 2016. Metabolism of oral turinabol by human steroid hormone-synthesizing cytochrome P450 enzymes. Drug Metab Dispos. 44:227–237.
  • Schiffer L, Muller AR, Hobler A, Brixius-Anderko S, Zapp J, Hannemann F, Bernhardt R. 2016. Biotransformation of the mineralocorticoid receptor antagonists spironolactone and canrenone by human CYP11B1 and CYP11B2: characterization of the products and their influence on mineralocorticoid receptor transactivation. J Steroid Biochem Mol Biol. 163:68–76.
  • Schuster I, Bernhardt R. 2007. Inhibition of cytochromes P450: Existing and new promising therapeutic targets. Drug Metab Rev. 39:481–499.
  • Shimada H, Kogure N, Noro E, Kudo M, Sugawara K, Sato I, Shimizu K, Kobayashi M, Suzuki D, Parvin R, et al. 2017. High glucose stimulates expression of aldosterone synthase (CYP11B2) and secretion of aldosterone in human adrenal cells. FEBS Open Biol. 7:1410–1421.
  • Song R, He Y, Murphy MB, Yeung LW, Yu RM, Lam MH, Lam PK, Hecker M, Giesy JP, Wu RS, et al. 2008. Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line. Chemosphere. 71:1888–1894.
  • Strushkevich N, Gilep AA, Shen L, Arrowsmith CH, Edwards AM, Usanov SA, Park HW. 2013. Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol Endocrinol. 27:315–324.
  • Suzuki D, Saito-Hakoda A, Ito R, Shimizu K, Parvin R, Shimada H, Noro E, Suzuki S, Fujiwara I, Kagechika H, et al. 2017. Suppressive effects of RXR agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion and blood pressure. PloS One. 12:e0181055.
  • Tsai YY, Rainey WE, Bollag WB. 2017. Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production. J Endocrinol. 232:R115–R129.
  • Ulmschneider S, Muller-Vieira U, Mitrenga M, Hartmann RW, Oberwinkler-Marchais S, Klein CD, Bureik M, Bernhardt R, Antes I, Lengauer T. 2005. Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: Potent inhibitors of aldosterone synthase. J Med Chem. 48:1796–1805.
  • Ulmschneider S, Negri M, Voets M, Hartmann RW. 2006. Development and evaluation of a pharmacophore model for inhibitors of aldosterone synthase (CYP11B2). Bioorg Med Chem Lett. 16:25–30.
  • Vasan RS, Evans JC, Larson MG, Wilson PW, Meigs JB, Rifai N, Benjamin EJ, Levy D. 2004. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. New Engl J Med. 351:33–41.
  • Voets M, Antes I, Scherer C, Muller-Vieira U, Biemel K, Barassin C, Marchais-Oberwinkler S, Hartmann RW. 2005. Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis. J Med Chem. 48:6632–6642.
  • Voets M, Antes I, Scherer C, Muller-Vieira U, Biemel K, Marchais-Oberwinkler S, Hartmann RW. 2006. Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. J Med Chem. 49:2222–2231.
  • Whaley-Connell A, Johnson MS, Sowers JR. 2010. Aldosterone: role in the cardiometabolic syndrome and resistant hypertension. Prog Cardiovasc Dis. 52:401–409.
  • White WB, Carr AA, Krause S, Jordan R, Roniker B, Oigman W. 2003. Assessment of the novel selective aldosterone blocker eplerenone using ambulatory and clinical blood pressure in patients with systemic hypertension. Am J Cardiol. 92:38–42.
  • Whitehead BR, Lo MM, Ali A, Park MK, Hoyt SB, Xiong Y, Cai J, Carswell E, Cooke A, MacLean J, et al. 2017. Imidazopyridyl compounds as aldosterone synthase inhibitors. Bioorg Med Chem Lett. 27:143–146.
  • Xing Y, Cohen A, Rothblat G, Sankaranarayanan S, Weibel G, Royer L, Francone OL, Rainey WE. 2011. Aldosterone production in human adrenocortical cells is stimulated by high-density lipoprotein 2 (HDL2) through increased expression of aldosterone synthase (CYP11B2). Endocrinology. 152:751–763.
  • Yin L, Hu Q, Emmerich J, Lo MM, Metzger E, Ali A, Hartmann RW. 2014. Novel pyridyl- or isoquinolinyl-substituted indolines and indoles as potent and selective aldosterone synthase inhibitors. J Med Chem. 57:5179–5189.

References

  • Ahmed S. 1999. A novel molecular modelling study of inhibitors of the 17α-hydroxylase component of the enzyme system 17α-hydroxylase/17,20-lyase (P-45017α). Bioorg Med Chem. 7:1487–1496.
  • Alyamani M, Li ZF, Berk M, Li JN, Tang JJ, Upadhyay S, Auchus RJ, Sharifi N. 2017. Steroidogenic metabolism of galeterone reveals a diversity of biochemical activities. Cell Chem Biol. 24:825–832.
  • Arlt W, Martens JW, Song M, Wang JT, Auchus RJ, Miller WL. 2002. Molecular evolution of adrenarche: structural and functional analysis of P450c17 from four primate species. Endocrinology. 143:4665–4672.
  • Asif AR, Ljubojevic M, Sabolic I, Shnitsar V, Metten M, Anzai N, Muller GA, Burckhardt G, Hagos Y. 2006. Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells. Am J Physiol Endocrinol Metab. 291:E1351–1359.
  • Attard G, Reid AH, Auchus RJ, Hughes BA, Cassidy AM, Thompson E, Oommen NB, Folkerd E, Dowsett M, Arlt W, et al. 2012. Clinical and biochemical consequences of CYP17A1 inhibition with abiraterone given with and without exogenous glucocorticoids in castrate men with advanced prostate cancer. J Clin Endocrinol Metab. 97:507–516.
  • Auchus ML, Auchus RJ. 2012. Human steroid biosynthesis for the oncologist. J Invest Med. 60:495–503.
  • Auchus RJ, Buschur EO, Chang AY, Hammer GD, Ramm C, Madrigal D, Wang G, Gonzalez M, Xu XS, Smit JW, et al. 2014. Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency. J Clin Endocrinol Metab. 99:2763–2770.
  • Auchus RJ, Lee TC, Miller WL. 1998. Cytochrome b5 augments the 17,20-lyase activity of human P450c17 without direct electron transfer. J Biol Chem. 273:3158–3165.
  • Auchus RJ, Miller WL. 2015. Chapter 12, P450 enzymes in steroid processing. In: Ortiz de Montellano PR, editor. Cytochrome P450: Structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 851–879.
  • Ayub M, Levell MJ. 1989. Inhibition of human adrenal steroidogenic enzymes in vitro by imidazole drugs including ketoconazole. J Steroid Biochem. 32:515–524.
  • Bird IM, Abbott DH. 2016. The hunt for a selective 17,20 lyase inhibitor; learning lessons from nature. J Steroid Biochem Mol Biol. 163:136–146.
  • Bonomo S, Hansen CH, Petrunak EM, Scott EE, Styrishave B, Jorgensen FS, Olsen L. 2016. Promising tools in prostate cancer research: selective non-steroidal cytochrome P450 17A1 inhibitors. Sci Rep. 6:29468.
  • Canton RF, Sanderson JT, Nijmeijer S, Bergman A, Letcher RJ, van den Berg M. 2006. In vitro effects of brominated flame retardants and metabolites on CYP17 catalytic activity: a novel mechanism of action? Toxicol Appl Pharmacol. 216:274–281.
  • Clement OO, Freeman CM, Hartmann RW, Handratta VD, Vasaitis TS, Brodie AM, Njar VC. 2003. Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy. J Med Chem. 46:2345–2351.
  • de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB, Jr., Saad F, et al. 2011. Abiraterone and increased survival in metastatic prostate cancer. New Engl J Med. 364:1995–2005.
  • De Coster R, Caers I, Coene MC, Amery W, Beerens D, Haelterman C. 1986. Effects of high dose ketoconazole therapy on the main plasma testicular and adrenal steroids in previously untreated prostatic cancer patients. Clin Endocrinol. 24:657–664.
  • DeVore NM, Scott EE. 2012. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001. Nature. 482:116–119.
  • Di Blasio AM, Voutilainen R, Jaffe RB, Miller WL. 1987. Hormonal regulation of messenger ribonucleic acids for P450scc (cholesterol side-chain cleavage enzyme) and P450c17 (17α-hydroxylase/17,20-lyase) in cultured human fetal adrenal cells. J Clin Endocrinol Metab. 65:170–175.
  • Doi J, Takemori H, Ohta M, Nonaka Y, Okamoto M. 2001. Differential regulation of 3β-hydroxysteroid dehydrogenase type II and 17α-hydroxylase/lyase P450 in human adrenocortical carcinoma cells by epidermal growth factor and basic fibroblast growth factor. J Endocrinol. 168:87–94.
  • Edwards BK, Noone AM, Mariotto AB, Simard EP, Boscoe FP, Henley SJ, Jemal A, Cho H, Anderson RN, Kohler BA, et al. 2014. Annual Report to the Nation on the Status of Cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer. 120:1290–1314.
  • Engelhardt D, Weber MM. 1994. Therapy of Cushing's syndrome with steroid biosynthesis inhibitors. J Steroid Biochem Mol Biol. 49:261–267.
  • Estrada DF, Skinner AL, Laurence JS, Scott EE. 2014. Human cytochrome P450 17A1 conformational selection: modulation by ligand and cytochrome b5. J Biol Chem. 289:14310–14320.
  • Ferraldeschi R, de Bono J. 2013. Agents that target androgen synthesis in castration-resistant prostate cancer. Cancer J. 19:34–42.
  • Furuta C, Noda S, Li C, Suzuki AK, Taneda S, Watanabe G, Taya K. 2008. Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line. Toxicol Appl Pharmacol. 229:109–120.
  • Geller DH, Auchus RJ, Mendonça BB, Miller WL. 1997. The genetic and functional basis of isolated 17,20-lyase deficiency. Nat Genet. 17:201–205.
  • Gilep AA, Sushko TA, Usanov SA. 2011. At the crossroads of steroid hormone biosynthesis: the role, substrate specificity and evolutionary development of CYP17. Biochim Biophys Acta. 1814:200–209.
  • Glister C, Satchell L, Michael AE, Bicknell AB, Knight PG. 2012. The anti-epileptic drug valproic acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro. PloS One. 7:e49553.
  • Gonzalez E, Guengerich FP. 2017. Kinetic processivity of the two-step oxidations of progesterone and pregnenolone to androgens by human cytochrome P450 17A1. J Biol Chem. 292:13168–13185.
  • Gonzalez E, Johnson KM, Pallan PS, Phan TTN, Zhang W, Lei L, Wawrzak Z, Yoshimoto FK, Egli M, Guengerich FP. 2018. Inherent steroid 17α,20-lyase activity in defunct cytochrome P450 17A enzymes. J Biol Chem. 293:541–566.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Guengerich FP, Yoshimoto FK. 2018. Formation and cleavage of C-C bonds by enzymatic oxidation reactions. Chem Rev. 118:6573–6655.
  • Handratta VD, Vasaitis TS, Njar VC, Gediya LK, Kataria R, Chopra P, Newman D, Jr., Farquhar R, Guo Z, Qiu Y, et al. 2005. Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. J Med Chem. 48:2972–2984.
  • Hasegawa E, Nakagawa S, Sato M, Tachikawa E, Yamato S. 2013. Effect of polyphenols on production of steroid hormones from human adrenocortical NCI-H295R cells. Biol Pharmaceut Bull. 36:228–237.
  • Hille UE, Hu Q, Vock C, Negri M, Bartels M, Muller-Vieira U, Lauterbach T, Hartmann RW. 2009. Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls. Eur J Med Chem. 44:2765–2775.
  • Hsu CH, Yang YC, Lian ST, Lee SC, Shin SJ, Tsai JH, Lin SR. 2001. Significantly increased cortisol secretion in normal adrenocortical cells transfected with K-ras mutants derived from human functional adrenocortical tumors. DNA Cell Biol. 20:231–238.
  • Hu Q, Yin L, Jagusch C, Hille UE, Hartmann RW. 2010. Isopropylidene substitution increases activity and selectivity of biphenylmethylene 4-pyridine type CYP17 inhibitors. J Med Chem. 53:5049–5053.
  • Ideyama Y, Kudoh M, Tanimoto K, Susaki Y, Nanya T, Nakahara T, Ishikawa H, Yoden T, Okada M, Fujikura T, et al. 1998. Novel nonsteroidal inhibitor of cytochrome P450(17α) (17α-hydroxylase/C17-20 lyase), YM116, decreased prostatic weights by reducing serum concentrations of testosterone and adrenal androgens in rats. Prostate. 37:10–18.
  • Idkowiak J, Randell T, Dhir V, Patel P, Shackleton CH, Taylor NF, Krone N, Arlt W. 2012. A missense mutation in the human cytochrome b5 gene causes 46,XY disorder of sex development due to true isolated 17,20 lyase deficiency. J Clin Endocrinol Metab. 97:E465–475.
  • Johansson MK, Sanderson JT, Lund BO. 2002. Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 16:113–121.
  • Kim B, Moon JY, Choi MH, Yang HH, Lee S, Lim KS, Yoon SH, Yu KS, Jang IJ, Cho JY. 2013. Global metabolomics and targeted steroid profiling reveal that rifampin, a strong human PXR activator, alters endogenous urinary steroid markers. J Proteome Res. 12:1359–1368.
  • Kisselev P, Tuckey RC, Woods ST, Triantopoulos T, Schwarz D. 1999. Enzymatic properties of vesicle-reconstituted human cytochrome P450SCC (CYP11A1) differences in functioning of the mitochondrial electron-transfer chain using human and bovine adrenodoxin and activation by cardiolipin. Eur J Biochem. 260:768–773.
  • Kok RC, Timmerman MA, Wolffenbuttel KP, Drop SL, de Jong FH. 2010. Isolated 17,20-lyase deficiency due to the cytochrome b5 mutation W27X. J Clin Endocrinol Metab. 95:994–999.
  • Leroux F. 2005. Inhibition of P450 17 as a new strategy for the treatment of prostate cancer. Curr Med Chem. 12:1623–1629.
  • Lin CJ, Cheng LC, Lin TC, Wang CJ, Li LA. 2014. Assessment of the potential of polyphenols as a CYP17 inhibitor free of adverse corticosteroid elevation. Biochem Pharmacol. 90:288–296.
  • Loriot Y, Bianchini D, Ileana E, Sandhu S, Patrikidou A, Pezaro C, Albiges L, Attard G, Fizazi K, De Bono JS, et al. 2013. Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Ann Oncol. 24:1807–1812.
  • Lundqvist J, Norlin M, Wikvall K. 2010. 1α,25-Dihydroxyvitamin D3 affects hormone production and expression of steroidogenic enzymes in human adrenocortical NCI-H295R cells. Biochim Biophys Acta. 1801:1056–1062.
  • Maitra A, Shirwalkar H. 2003. Congenital adrenal hyperplasia: Biochemical and molecular perspectives. Indian J Exp Biol. 41:701–709.
  • Malikova J, Brixius-Anderko S, Udhanea SS, Parween S, Dick B, Bernhardt R, Pandey AV. 2017. CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2. J Steroid Biochem Mol Biol. 174:192–200.
  • Mesiano S, Katz SL, Lee JY, Jaffe RB. 1997. Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen regulation. J Clin Endocrinol Metab. 82:1390–1396.
  • Miller WL, Auchus RJ. 2011. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocrin Rev. 32:81–151.
  • Naffin-Olivos JL, Auchus RJ. 2006. Human cytochrome b5 requires residues E48 and E49 to stimulate the 17,20-lyase activity of cytochrome P450c17. Biochemistry. 45:755–762.
  • Nelson-DeGrave VL, Wickenheisser JK, Cockrell JE, Wood JR, Legro RS, Strauss JF, 3rd, McAllister JM. 2004. Valproate potentiates androgen biosynthesis in human ovarian theca cells. Endocrinology. 145:799–808.
  • Niwa T, Fujimoto M, Kishimoto K, Yabusaki Y, Ishibashi F, Katagiri M. 2001. Metabolism and interaction of bisphenol A in human hepatic cytochrome P450 and steroidogenic CYP17. Biol Pharm Bull. 24:1064–1067.
  • Njar VC, Kato K, Nnane IP, Grigoryev DN, Long BJ, Brodie AM. 1998. Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17α-hydroxylase-C17,20-lyase (P45017α): potential agents for the treatment of prostate cancer. J Med Chem. 41:902–912.
  • Ogo A, Haji M, Ohashi M, Nawata H. 1991. Markedly increased expression of cytochrome P-450 17α-hydroxylase (P-450c17) mRNA in adrenocortical adenomas from patients with Cushing's syndrome. Mol Cell Endocrinol. 80:83–89.
  • Ohlsson A, Ulleras E, Oskarsson A. 2009. A biphasic effect of the fungicide prochloraz on aldosterone, but not cortisol, secretion in human adrenal H295R cells–underlying mechanisms. Toxicol Lett. 191:174–180.
  • Pallan PS, Nagy LD, Lei L, Gonzalez E, Kramlinger VM, Azumaya CM, Wawrzak Z, Waterman MR, Guengerich FP, Egli M. 2015. Structural and kinetic basis of steroid 17α,20-lyase activity in teleost fish cytochrome P450 17A1 and its absence in cytochrome P450 17A2. J Biol Chem. 290:3248–3268.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Petrunak EM, DeVore NM, Porubsky PR, Scott EE. 2014. Structures of human steroidogenic cytochrome P450 17A1 with substrates. J Biol Chem. 289:32952–32964.
  • Petrunak EM, Rogers SA, Aube J, Scott EE. 2017. Structural and functional evaluation of clinically relevant inhibitors of steroidogenic cytochrome P450 17A1. Drug Metab Dispos. 45:635–645.
  • Pia A, Vignani F, Attard G, Tucci M, Bironzo P, Scagliotti G, Arlt W, Terzolo M, Berruti A. 2013. Strategies for managing ACTH dependent mineralocorticoid excess induced by abiraterone. Cancer Treatment Rev. 39:966–973.
  • Pikuleva IA, Mast N, Liao WL, Turko IV. 2008. Studies of membrane topology of mitochondrial cholesterol hydroxylases CYPs 27A1 and 11A1. Lipids. 43:1127–1132.
  • Pinto-Bazurco Mendieta MA, Negri M, Jagusch C, Muller-Vieira U, Lauterbach T, Hartmann RW. 2008. Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer. J Med Chem. 51:5009–5018.
  • Qin KN, Rosenfield RL. 1998. Role of cytochrome P450c17 in polycystic ovary syndrome. Mol Cell Endocrinol. 145:111–121.
  • Rege J, Nishimoto HK, Nishimoto K, Rodgers RJ, Auchus RJ, Rainey WE. 2015. Bone morphogenetic protein-4 (BMP4): a paracrine regulator of human adrenal C19 steroid synthesis. Endocrinology. 156:2530–2540.
  • Sawetawan C, Carr BR, McGee E, Bird IM, Hong TL, Rainey WE. 1996. Inhibin and activin differentially regulate androgen production and 17α-hydroxylase expression in human ovarian thecal-like tumor cells. J Endocrinol. 148:213–221.
  • Schroeder RL, Tram P, Liu J, Foroozesh M, Sridhar J. 2016. Novel functionalized 5-(phenoxymethyl)-1,3-dioxane analogs exhibiting cytochrome P450 inhibition: a patent evaluation WO2015048311 (A1). Exp Opin Ther Pat. 26:139–147.
  • Sherbet DP, Tiosano D, Kwist KM, Hochberg Z, Auchus RJ. 2003. CYP17 mutation E305G causes isolated 17,20-lyase deficiency by selectively altering substrate binding. J Biol Chem. 278:48563–48569.
  • Sohl CD, Guengerich FP. 2010. Kinetic analysis of the three-step steroid aromatase reaction of human cytochrome P450 19A1. J Biol Chem. 285:17734–17743.
  • Song R, He Y, Murphy MB, Yeung LW, Yu RM, Lam MH, Lam PK, Hecker M, Giesy JP, Wu RS, et al. 2008. Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line. Chemosphere. 71:1888–1894.
  • Stein MN, Patel N, Bershadskiy A, Sokoloff A, Singer EA. 2014. Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer. Asian J Androl. 16:387–400.
  • Strauss JF, 3rd. 2003. Some new thoughts on the pathophysiology and genetics of polycystic ovary syndrome. Ann NY Acad Sci. 997:42–48.
  • Van Den Akker EL, Koper JW, Boehmer AL, Themmen AP, Verhoef-Post M, Timmerman MA, Otten BJ, Drop SL, De Jong FH. 2002. Differential inhibition of 17α-hydroxylase and 17,20-lyase activities by three novel missense CYP17 mutations identified in patients with P450c17 deficiency [Case Reports]. J Clin Endocrinol Metab. 87:5714–5721.
  • van Duursen MB, Nijmeijer SM, Ruchirawat S, van den Berg M. 2010. Chemopreventive actions by enterolactone and 13 VIOXX-related lactone derivatives in H295R human adrenocortical carcinoma cells. Toxicol Lett. 192:271–277.
  • van Koetsveld PM, Vitale G, Feelders RA, Waaijers M, Sprij-Mooij DM, de Krijger RR, Speel EJ, Hofland J, Lamberts SW, de Herder WW, et al. 2013. Interferon-β is a potent inhibitor of cell growth and cortisol production in vitro and sensitizes human adrenocortical carcinoma cells to mitotane. Endocr Relat Cancer. 20:443–454.
  • Wickenheisser JK, Nelson-DeGrave VL, Hendricks KL, Legro RS, Strauss JF, 3rd, McAllister JM. 2005. Retinoids and retinol differentially regulate steroid biosynthesis in ovarian theca cells isolated from normal cycling women and women with polycystic ovary syndrome. J Clin Endocrinol Metab. 90:4858–4865.
  • Yadav R, Petrunak EM, Estrada DF, Scott EE. 2017. Structural insights into the function of steroidogenic cytochrome P450 17A1. Mol Cell Endocrinol. 441:68–75.
  • Yamaoka M, Hara T, Hitaka T, Kaku T, Takeuchi T, Takahashi J, Asahi S, Miki H, Tasaka A, Kusaka M. 2012. Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J Steroid Biochem Mol Biol. 129:115–128.
  • Yin L, Hu Q. 2014. CYP17 inhibitors–abiraterone, C17,20-lyase inhibitors and multi-targeting agents. Nat Rev Urol. 11:32–42.
  • Yoshimoto FK, Gonzalez E, Auchus RJ, Guengerich FP. 2016. Mechanism of 17α,20-lyase and new hydroxylation reactions of human cytochrome P450 17A1: 18O labeling and oxygen surrogate evidence for a role of a perferryl oxygen. J Biol Chem. 291:17143–17164.
  • Zuber MX, Simpson ER, Waterman MR. Regulation of cytochrome P-450(17α) activity and synthesis in bovine adrenocortical cells. 1985. Ann NY Acad Sci. 458:252–261.

References

  • Abul-Hajj YJ. 1983. Studies on the mechanism of action of the aromatase inhibitor, 4-hydroxyandrostenedione. Steroids. 41:783–790.
  • Adlercreutz H, Bannwart C, Wahala K, Makela T, Brunow G, Hase T, Arosemena PJ, Kellis JT, Jr., Vickery LE. 1993. Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. J Steroid Biochem Mol Biol. 44:147–153.
  • Ahmad I, Shagufta. 2015. Recent developments in steroidal and nonsteroidal aromatase inhibitors for the chemoprevention of estrogen-dependent breast cancer. Eur J Med Chem. 102:375–386.
  • Ahmed S, Amanuel Y. 2000. Synthesis and biochemical evaluation of novel inhibitors of aromatase (AR) using an enhanced representation of the active site of AR derived from the consideration of the reaction mechanism. Biochem Biophys Res Commun. 267:356–361.
  • Ahmed S, Smith JH, Nicholls PJ, Whomsley R, Cariuk P. 1995. Synthesis and biological evaluation of imidazole based compounds as cytochrome P-450 inhibitors. Drug Design Discov. 13:27–41.
  • Akhtar M, Calder MR, Corina DL, Wright JN. 1982. Mechanistic studies on C-19 demethylation in oestrogen biocynthesis. Biochem J. 201:569–580.
  • Akhtar M, Corina D, Pratt J, Smith T. 1976. Studies on the removal of C-19 in oestrogen biosynthesis using 18O2. J Chem Soc Chem Commun. 854–856.
  • Almstrup K, Fernandez MF, Petersen JH, Olea N, Skakkebaek NE, Leffers H. 2002. Dual effects of phytoestrogens result in U-shaped dose-response curves. Environ Health Perspect. 110:743–748.
  • Andersen HR, Vinggaard AM, Rasmussen TH, Gjermandsen IM, Bonefeld-Jørgensen EC. 2002. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Toxicol Appl Pharmacol. 179:1–12.
  • Andrews WJ, Winnett G, Rehman F, Shanmugasundaram P, Hagen D, Schrey MP. 2005. Aromatase inhibition by 15-deoxy-prostaglandin J2 (15-dPGJ2) and N-(4-hydroxyphenyl)-retinamide (4HPR) is associated with enhanced ceramide production. J Steroid Biochem Mol Biol. 94:159–165.
  • Ayub M, Levell MJ. 1988. Structure-activity relationships of the inhibition of human placental aromatase by imidazole drugs including ketoconazole. J Steroid Biochem. 31:65–72.
  • Ayub M, Levell MJ. 1990. The inhibition of human prostatic aromatase activity by imidazole drugs including ketoconazole and 4-hydroxyandrostenedione. Biochem Pharmacol. 40:1569–1575.
  • Barrera D, Avila E, Hernandez G, Halhali A, Biruete B, Larrea F, Diaz L. 2007. Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. J Steroid Biochem Mol Biol. 103:529–532.
  • Bednarski PJ, Hartmann RW. 1993. Synthesis and evaluation of sulfur-containing glutethimide derivatives for aromatase and desmolase inhibitory activity. Archiv Pharm. 326:391–394.
  • Benachour N, Moslemi S, Sipahutar H, Seralini GE. 2007. Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination. Toxicol Appl Pharmacol. 222:129–140.
  • Blanco JG, Gil RR, Alvarez CI, Patrito LC, Genti-Raimondi S, Flury A. 1997. A novel activity for a group of sesquiterpene lactones: inhibition of aromatase. FEBS Lett. 409:396–400.
  • Boeddinghaus IM, Dowsett M. 2001. Comparative clinical pharmacology and pharmacokinetic interactions of aromatase inhibitors. J Steroid Biochem Mol Biol. 79:85–91.
  • Bois FY, Golbamaki-Bakhtyari N, Kovarich S, Tebby C, Gabb HA, Lemazurier E. 2017. High-throughput analysis of ovarian cycle disruption by mixtures of aromatase inhibitors. Environ Health Perspect. 125:077012.
  • Brueggemeier RW, Diaz-Cruz ES, Li PK, Sugimoto Y, Lin YC, Shapiro CL. 2005. Translational studies on aromatase, cyclooxygenases, and enzyme inhibitors in breast cancer. J Steroid Biochem Mol Biol. 95:129–136.
  • Bulun SE, Sebastian S, Takayama K, Suzuki T, Sasano H, Shozu M. 2003. The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters. J Steroid Biochem Mol Biol. 86:219–224.
  • Campbell DR, Kurzer MS. 1993. Flavonoid inhibition of aromatase enzyme activity in human preadipocytes. J Steroid Biochem Mol Biol. 46:381–388.
  • Cantón RF, Sanderson JT, Letcher RJ, Bergman A, van den Berg M. 2005. Inhibition and induction of aromatase (CYP19) activity by brominated flame retardants in H295R human adrenocortical carcinoma cells. Toxicol Sci. 88:447–455.
  • Cantón RF, Scholten DE, Marsh G, de Jong PC, van den Berg M. 2008. Inhibition of human placental aromatase activity by hydroxylated polybrominated diphenyl ethers (OH-PBDEs). Toxicol Appl Pharmacol. 227:68–75.
  • Caporuscio F, Rastelli G, Imbriano C, Del Rio A. 2011. Structure-based design of potent aromatase inhibitors by high-throughput docking. J Med Chem. 54:4006–4017.
  • Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER. 1997. Effect of testosterone and estradiol in a man with aromatase deficiency. New Engl J Med. 337:91–95.
  • Caspi E, Arunachalam T, Nelson PA. 1986. Biosynthesis of estrogens: aromatization of (19R)-, (19S)-, and (19S)-[19-3H,2H,1H]-3β-hydroxyandrost-5-en-17-ones by human placental aromatase. J Am Chem Soc. 108:1847–1852.
  • Chauhan B, Yu C, Krantis A, Scott I, Arnason JT, Marles RJ, Foster BC. 2007. In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P-glycoprotein. Canad J Physiol Pharmacol. 85:1099–1107.
  • Chen D, Reierstad S, Lin Z, Lu M, Brooks C, Li N, Innes J, Bulun SE. 2007. Prostaglandin E2 induces breast cancer related aromatase promoters via activation of p38 and c-Jun NH2-terminal kinase in adipose fibroblasts. Cancer Res. 67:8914–8922.
  • Chen L, Chen X, Chen X, Hu Z, Li X, Su Y, Li X, Ge RS. 2017. Ziram inhibits aromatase activity in human placenta and JEG-3 cell line. Steroids. 128:114–119.
  • Chen S, Oh SR, Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D. 2006. Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus). Cancer Res. 66:12026–12034.
  • Chen Y, Cai S, Wang J, Xu M. 2015. Valproic acid-induced histone acetylation suppresses CYP19 gene expression and inhibits the growth and survival of endometrial stromal cells. Int J Mol Med. 36:725–732.
  • Chottanapund S, Van Duursen MB, Navasumrit P, Hunsonti P, Timtavorn S, Ruchirawat M, Van den Berg M. 2014. Anti-aromatase effect of resveratrol and melatonin on hormonal positive breast cancer cells co-cultured with breast adipose fibroblasts. Toxicol In Vitro. 28:1215–1221.
  • Chottanapund S, Van Duursen MBM, Zwartsen A, Timtavorn S, Navasumrit P, Kittakoop P, Sureram S, Ruchirawat M, Van den Berg M. 2017. Depsidones inhibit aromatase activity and tumor cell proliferation in a co-culture of human primary breast adipose fibroblasts and T47D breast tumor cells. Toxicol Rep. 4:165–171.
  • Chu PW, Yang ZJ, Huang HH, Chang AA, Cheng YC, Wu GJ, Lan HC. 2018. Low-dose bisphenol A activates the ERK signaling pathway and attenuates steroidogenic gene expression in human placental cells. Biol Reprod. 98:250–258.
  • Clyne CD, Kovacic A, Speed CJ, Zhou J, Pezzi V, Simpson ER. 2004. Regulation of aromatase expression by the nuclear receptor LRH-1 in adipose tissue. Mol Cell Endocrinol. 215:39–44.
  • Conley A, Hinshelwood M. 2001. Mammalian aromatases. Reproduction. 121:685–695.
  • Conley A, Mapes S, Corbin CJ, Greger D, Graham S. 2002. Structural determinants of aromatase cytochrome P450 inhibition in substrate recognition site-1. Mol Endocrinol. 16:1456–1468.
  • Couzinet B, Meduri G, Lecce MG, Young J, Brailly S, Loosfelt H, Milgrom E, Schaison G. 2001. The postmenopausal ovary is not a major androgen-producing gland. J Clin Endocrinol Metab. 86:5060–5066.
  • Cui J, Wang Y, Dong Q, Wu S, Xiao X, Hu J, Chai Z, Zhang Y. 2011. Morphine protects against intracellular amyloid toxicity by inducing estradiol release and upregulation of Hsp70. J Neurosci. 31:16227–16240.
  • Di Nardo G, Cimicata G, Baravalle R, Dell'Angelo V, Ciaramella A, Catucci G, Ugliengo P, Gilardi G. 2018. Working at the membrane interface: ligand-induced changes in dynamic conformation and oligomeric structure in human aromatase. Biotechnol Appl Biochem. 65:46–53.
  • Diaz-Cruz ES, Shapiro CL, Brueggemeier RW. 2005. Cyclooxygenase inhibitors suppress aromatase expression and activity in breast cancer cells. J Clin Endocrinol Metab. 90:2563–2570.
  • Diaz-Thomas A, Shulman D. 2010. Use of aromatase inhibitors in children and adolescents: What's new? Curr Opin Pediatr. 22:501–507.
  • Dieudonné MN, Sammari A, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R. 2006. Sex steroids and leptin regulate 11β-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: Sex specificities. J Steroid Biochem Mol Biol. 99:189–196.
  • Dong Y, Mao B, Li L, Guan H, Su Y, Li X, Lian Q, Huang P, Ge RS. 2016. Gossypol enantiomers potently inhibit human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase activities. Fitoterapia. 109:132–137.
  • Drenth HJ, Bouwman CA, Seinen W, Van den Berg M. 1998. Effects of some persistent halogenated environmental contaminants on aromatase (CYP19) activity in the human choriocarcinoma cell line JEG-3. Toxicol Appl Pharmacol. 148:50–55.
  • Dunkel L. 2006. Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol. 254–255:207–216.
  • Eng ET, Williams D, Mandava U, Kirma N, Tekmal RR, Chen S. 2001. Suppression of aromatase (estrogen synthetase) by red wine phytochemicals. Breast Cancer Res Treat. 67:133–146.
  • Eng ET, Williams D, Mandava U, Kirma N, Tekmal RR, Chen S. 2002. Anti-aromatase chemicals in red wine. Ann NY Acad Sci. 963:239–246.
  • Eng ET, Ye J, Williams D, Phung S, Moore RE, Young MK, Gruntmanis U, Braunstein G, Chen S. 2003. Suppression of estrogen biosynthesis by procyanidin dimers in red wine and grape seeds. Cancer Res. 63:8516–8522.
  • Enjuanes A, Garcia-Giralt N, Supervia A, Nogues X, Ruiz-Gaspa S, Bustamante M, Mellibovsky L, Grinberg D, Balcells S, Diez-Perez A. 2005. Functional analysis of the I.3, I.6, pII and I.4 promoters of CYP19 (aromatase) gene in human osteoblasts and their role in vitamin D and dexamethasone stimulation. Eur J Endocrinol. 153:981–988.
  • Ertas M, Sahin Z, Berk B, Yurttas L, Biltekin SN, Demirayak S. 2018. Pyridine-substituted thiazolylphenol derivatives: synthesis, modeling studies, aromatase inhibition, and antiproliferative activity evaluation. Arch Pharm (Weinheim). 351(3–4):e1700272.
  • Ferris JA, Geffner ME. 2017. Are aromatase inhibitors in boys with predicted short stature and/or rapidly advancing bone age effective and safe? J Pediat Endocrinol Metab. 30:311–317.
  • Filleur F, Le Bail JC, Duroux JL, Simon A, Chulia AJ. 2001. Antiproliferative, anti-aromatase, anti-17β-HSD and antioxidant activities of lignans isolated from Myristica argentea. Planta Med. 67:700–704.
  • Fiorelli G, Picariello L, Martineti V, Tonelli F, Brandi ML. 1999. Estrogen synthesis in human colon cancer epithelial cells. J Steroid Biochem Mol Biol. 71:223–230.
  • Fisher CR, Graves KH, Parlow AF, Simpson ER. 1998. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci USA. 95:6965–6970.
  • Geelen JA, Deckers GH, van der Wardt JT, Loozen HJ, Tax LJ, Kloosterboer HJ. 1991. Selection of 19-(ethyldithio)-androst-4-ene-3,17-dione (ORG 30958): a potent aromatase inhibitor in vivo. J Steroid Biochem Mol Biol. 38:181–188.
  • Ghosh D, Egbuta C, Lo J. 2018. Testosterone complex and non-steroidal ligands of human aromatase. J Steroid Biochem Mol Biol. 181:11–19.
  • Ghosh D, Griswold J, Erman M, Pangborn W. 2009. Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature. 457:219–223.
  • Ghosh D, Lo J, Morton D, Valette D, Xi J, Griswold J, Hubbell S, Egbuta C, Jiang W, An J, et al. 2012. Novel aromatase inhibitors by structure-guided design. J Med Chem. 55:8464–8476.
  • Glister C, Satchell L, Michael AE, Bicknell AB, Knight PG. 2012. The anti-epileptic drug valproic acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro. PloS One. 7:e49553.
  • Görlitzer K, Bonnekessel C, Jones PG, Palusczak A, Hartmann RW. 2006. Derivatives of exemestane–synthesis and evaluation of aromatase inhibition. Die Pharmazie. 61:575–581. Germany.
  • Goto J, Fishman J. 1977. Participation of a nonenzymatic transformation in the biosynthesis of estrogens from androgens. Science. 195:80–81.
  • Grube BJ, Eng ET, Kao YC, Kwon A, Chen S. 2001. White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. J Nutr. 131:3288–3293.
  • Guo J, Yuan Y, Lu D, Du B, Xiong L, Shi J, Yang L, Liu W, Yuan X, Zhang G, et al. 2014. Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19). Toxicol Appl Pharmacol. 279:23–32.
  • Hackett JC, Brueggemeier RW, Hadad CM. 2005. The final catalytic step of cytochrome P450 aromatase: a density functional theory study. J Am Chem Soc. 127:5224–5237.
  • Hadizadeh F, Kalalinia F, Jouya M, Komachal AK, Mohammad AS, Karimi G, Behravan J, Abnous K, Etemad L, Kamali H. 2018. Design, synthesis, and biological evaluation of new azole derivatives as potent aromatase inhibitors with potential effects against breast cancer. Anticancer Agents Med Chem. DOI:10.2174/1871520618666180116105858
  • Hahn EF, Fishman J. 1984. Immunological probe of estrogen biosynthesis. Evidence for the 2β-hydroxylative pathway in aromatization of androgens. J Biol Chem. 259:1689–1694.
  • Hartmann RW, Bayer H, Grun G. 1994. Aromatase inhibitors. Syntheses and structure-activity studies of novel pyridyl-substituted indanones, indans, and tetralins. J Med Chem. 37:1275–1281.
  • Hartmann RW, Bayer H, Grun G, Sergejew T, Bartz U, Mitrenga M. 1995. Pyridyl-substituted tetrahydrocyclopropa[a]naphthalenes: highly active and selective inhibitors of P450arom. J Med Chem. 38:2103–2111.
  • Heneweer M, van den Berg M, Sanderson JT. 2004. A comparison of human H295R and rat R2C cell lines as in vitro screening tools for effects on aromatase. Toxicol Lett. 146:183–194.
  • Hirani VN, Raucy JL, Lasker JM. 2004. Conversion of the HIV protease inhibitor nelfinavir to a bioactive metabolite by human liver CYP2C19. Drug Metab Dispos. 32:1462–1467.
  • Hong Y, Yu B, Sherman M, Yuan YC, Zhou D, Chen S. 2007. Molecular basis for the aromatization reaction and exemestane-mediated irreversible inhibition of human aromatase. Mol Endocrinol. 21:401–414.
  • Huang BM, Hsiao KY, Chuang PC, Wu MH, Pan HA, Tsai SJ. 2004. Upregulation of steroidogenic enzymes and ovarian 17β-estradiol in human granulosa-lutein cells by Cordyceps sinensis mycelium. Biol Reprod. 70:1358–1364.
  • Ibrahim AR, Abul-Hajj YJ. 1990. Aromatase inhibition by flavonoids. J Steroid Biochem Mol Biol. 37:257–260.
  • Jacobsen NW, Halling-Sorensen B, Birkved FK. 2008. Inhibition of human aromatase complex (CYP19) by antiepileptic drugs. Toxicol In Vitro. 22:146–153.
  • Jeong HJ, Chang LC, Kim HK, Kim IH, Kinghorn AD, Pezzuto JM. 2000. Aromatase inhibitors from Isodon excisus var. coreanus. Archiv Pharmacal Res. 23:243–245.
  • Jeong HJ, Shin YG, Kim IH, Pezzuto JM. 1999. Inhibition of aromatase activity by flavonoids. Archiv Pharmacal Res. 22:309–312.
  • Jiang B, Kamat A, Mendelson CR. 2000. Hypoxia prevents induction of aromatase expression in human trophoblast cells in culture: potential inhibitory role of the hypoxia-inducible transcription factor MASH-2 (mammalian achaete-scute homologous protein-2). Mol Endocrinol. 14:1661–1673.
  • Jiang B, Mendelson CR. 2005. O2 enhancement of human trophoblast differentiation and hCYP19 (aromatase) gene expression are mediated by proteasomal degradation of USF1 and USF2. Mol Cell Biol. 25:8824–8833.
  • Jin UH, Kim KS, Park SY, Chung KH, Kim DS, Chang YC, Kim CH. 2006. Effect of Buthus martensi Karsch on aromatase activity and cytokine-inducted NOS and NO production in osteoblasts and leukaemic cell line FLG 29.1. Immunopharmacol Immunotoxicol. 28:241–258.
  • Johnston JO, Wright CL, Holbert GW, Benson HD. 1990. Enzyme inactivation by potential metabolites of an aromatase-activated inhibitor (MDL 18,962). J Enz Inhib. 4:137–142.
  • Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek NE. 1994. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab. 78:744–752.
  • Kamat A, Smith ME, Shelton JM, Richardson JA, Mendelson CR. 2005. Genomic regions that mediate placental cell-specific and developmental regulation of human Cyp19 (aromatase) gene expression in transgenic mice. Endocrinology. 146:2481–2488.
  • Kang H, Xiao X, Huang C, Yuan Y, Tang D, Dai X, Zeng X. 2018. Potent aromatase inhibitors and molecular mechanism of inhibitory action. Eur J Med Chem. 143:426–437.
  • Kellis JT, Jr., Nesnow S, Vickery LE. 1986. Inhibition of aromatase cytochrome P-450 (estrogen synthetase) by derivatives of α-naphthoflavone. Biochem Pharmacol. 35:2887–2891.
  • Kellis JT, Jr., Vickery LE. 1984. Inhibition of human estrogen synthetase (aromatase) by flavones. Science. 225:1032–1034.
  • Kelloff GJ, Lubet RA, Lieberman R, Eisenhauer K, Steele VE, Crowell JA, Hawk ET, Boone CW, Sigman CC. 1998. Aromatase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev. 7:65–78.
  • Khatri Y, Luthra A, Duggal R, Sligar SG. 2014. Kinetic solvent isotope effect in steady-state turnover by CYP19A1 suggests involvement of Compound 1 for both hydroxylation and aromatization steps. FEBS Lett. 588:3117–3122.
  • Kim B, Moon JY, Choi MH, Yang HH, Lee S, Lim KS, Yoon SH, Yu KS, Jang IJ, Cho JY. 2013. Global metabolomics and targeted steroid profiling reveal that rifampin, a strong human PXR activator, alters endogenous urinary steroid markers. J Proteome Res. 12:1359–1368.
  • Kitawaki J, Yamamoto T, Urabe M, Tamura T, Inoue S, Honjo H, Okada H. 1990. Selective aromatase inhibition by pyridoglutethimide, an analogue of aminoglutethimide. Acta Endocrinol. 122:592–598.
  • Kjeldsen LS, Ghisari M, Bonefeld-Jørgensen EC. 2013. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity. Toxicol Appl Pharmacol. 272:453–464.
  • Kümler I, Knoop AS, Jessing CA, Ejlertsen B, Nielsen DL. 2016. Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant. ESMO Open. 1:e000062.
  • Lacey M, Bohday J, Fonseka SM, Ullah AI, Whitehead SA. 2005. Dose-response effects of phytoestrogens on the activity and expression of 3β-hydroxysteroid dehydrogenase and aromatase in human granulosa-luteal cells. J Steroid Biochem Mol Biol. 96:279–286.
  • Laville N, Balaguer P, Brion F, Hinfray N, Casellas C, Porcher JM, Ait-Aissa S. 2006. Modulation of aromatase activity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line. Toxicology. 228:98–108.
  • Le Bail JC, Champavier Y, Chulia AJ, Habrioux G. 2000. Effects of phytoestrogens on aromatase, 3β and 17β-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Sci. 66:1281–1291.
  • Le Bail JC, Laroche T, Marre-Fournier F, Habrioux G. 1998. Aromatase and 17β-hydroxysteroid dehydrogenase inhibition by flavonoids. Cancer Lett. 133:101–106.
  • Le Bail JC, Pouget C, Fagnere C, Basly JP, Chulia AJ, Habrioux G. 2001. Chalcones are potent inhibitors of aromatase and 17β-hydroxysteroid dehydrogenase activities. Life Sci. 68:751–761.
  • Letcher RJ, van Holsteijn I, Drenth HJ, Norstrom RJ, Bergman A, Safe S, Pieters R, van den Berg M. 1999. Cytotoxicity and aromatase (CYP19) activity modulation by organochlorines in human placental JEG-3 and JAR choriocarcinoma cells. Toxicol Appl Pharmacol. 160:10–20.
  • Li LA. 2007. Polychlorinated biphenyl exposure and CYP19 gene regulation in testicular and adrenocortical cell lines. Toxicol In Vitro. 21:1087–1094.
  • Linardi A, Damiani D, Longui CA. 2017. The use of aromatase inhibitors in boys with short stature: what to know before prescribing? Arch Endocrinol Metab. 61:391–397.
  • Lønning PE, Eikesdal HP. 2013. Aromatase inhibition 2013: Clinical state of the art and questions that remain to be solved. Endocr Relat Cancer. 20:R183–201.
  • Lou YR, Murtola T, Tuohimaa P. 2005. Regulation of aromatase and 5α-reductase by 25-hydroxyvitamin D3, 1α,25-dihydroxyvitamin D3, dexamethasone and progesterone in prostate cancer cells. J Steroid Biochem Mol Biol. 94:151–157.
  • Lu D, Yang L, Li Q, Gao X, Wang F, Zhang G. 2012. Egonol gentiobioside and egonol gentiotrioside from Styrax perkinsiae promote the biosynthesis of estrogen by aromatase. Eur J Pharmacol. 691:275–282.
  • Lu DF, Yang LJ, Wang F, Zhang GL. 2012. Inhibitory effect of luteolin on estrogen biosynthesis in human ovarian granulosa cells by suppression of aromatase (CYP19). J Agri Food Chem. 60:8411–8418.
  • Lu WJ, Desta Z, Flockhart DA. 2012. Tamoxifen metabolites as active inhibitors of aromatase in the treatment of breast cancer. Breast Cancer Res Treat. 131:473–481.
  • Lu WJ, Xu C, Pei Z, Mayhoub AS, Cushman M, Flockhart DA. 2012. The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Breast Cancer Res Treat. 133:99–109.
  • Magistrato A, Sgrignani J, Krause R, Cavalli A. 2017. Single or multiple access channels to the CYP450s active site? An answer from free energy simulations of the human aromatase enzyme. J Phys Chem Lett. 8:2036–2042.
  • Maiti A, Cuendet M, Croy VL, Endringer DC, Pezzuto JM, Cushman M. 2007. Synthesis and biological evaluation of (±)-abyssinone II and its analogues as aromatase inhibitors for chemoprevention of breast cancer. J Med Chem. 50:2799–2806.
  • Marchand P, Le Borgne M, Palzer M, Le Baut G, Hartmann RW. 2003. Preparation and pharmacological profile of 7-(α-azolylbenzyl)-1H-indoles and indolines as new aromatase inhibitors. Bioorg Med Chem Lett. 13:1553–1555.
  • Mauger JW. 1989. The impact of innovative drug delivery systems on drug toxicity. J Toxicol Clin Toxicol. 27:v–vii.
  • Mauras N. 2011. Strategies for maximizing growth in puberty in children with short stature. Ped Clinics North Amer. 58:1167–1179.
  • McCammon KM, Panda SP, Xia C, Kim JJ, Moutinho D, Kranendonk M, Auchus RJ, Lafer EM, Ghosh D, Martasek P, et al. 2016. Instability of the human cytochrome P450 reductase A287P variant is the major contributor to its Antley-Bixler Syndrome-like phenotype. J Biol Chem. 291:20487–20502.
  • McGrath N, O'Grady MJ. 2015. Aromatase inhibitors for short stature in male children and adolescents. Cochrane Database Syst Rev. (10):CD010888.
  • McNulty J, Keskar K, Crankshaw DJ, Holloway AC. 2014. Discovery of a new class of cinnamyl-triazole as potent and selective inhibitors of aromatase (cytochrome P450 19A1). Bioorg Med Chem Lett. 24:4586–4589.
  • McNulty J, Nair JJ, Bollareddy E, Keskar K, Thorat A, Crankshaw DJ, Holloway AC, Khan G, Wright GD, Ejim L. 2009. Isolation of flavonoids from the heartwood and resin of Prunus avium and some preliminary biological investigations. Phytochemistry. 70:2040–2046.
  • Means GD, Kilgore MW, Mahendroo MS, Mendelson CR, Simpson ER. 1991. Tissue-specific promoters regulate aromatase cytochrome P450 gene expression in human ovary and fetal tissues. Mol Endocrinol. 5:2005–2013.
  • Mendelson CR, Jiang B, Shelton JM, Richardson JA, Hinshelwood MM. 2005. Transcriptional regulation of aromatase in placenta and ovary. J Steroid Biochem Mol Biol. 95:25–33.
  • Morinaga H, Yanase T, Nomura M, Okabe T, Goto K, Harada N, Nawata H. 2004. A benzimidazole fungicide, benomyl, and its metabolite, carbendazim, induce aromatase activity in a human ovarian granulose-like tumor cell line (KGN). Endocrinology. 145:1860–1869.
  • Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K. 1995. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 80:3689–3698.
  • Mu YM, Yanase T, Nishi Y, Hirase N, Goto K, Takayanagi R, Nawata H. 2000. A nuclear receptor system constituted by RAR and RXR induces aromatase activity in MCF-7 human breast cancer cells. Mol Cell Endocrinol. 166:137–145.
  • Mu YM, Yanase T, Nishi Y, Waseda N, Oda T, Tanaka A, Takayanagi R, Nawata H. 2000. Insulin sensitizer, troglitazone, directly inhibits aromatase activity in human ovarian granulosa cells. Biochem Biophys Res Commun. 271:710–713.
  • Muralimanoharan S, Kwak YT, Mendelson CR. 2018. Redox-sensitive transcription factor NRF2 enhances trophoblast differentiation via induction of miR-1246 and aromatase. Endocrinology. 159:2022–2033.
  • Nativelle-Serpentini C, Richard S, Séralini GE, Sourdaine P. 2003. Aromatase activity modulation by lindane and bisphenol-A in human placental JEG-3 and transfected kidney E293 cells. Toxicol In Vitro. 17:413–422.
  • Neunzig J, Milhim M, Schiffer L, Khatri Y, Zapp J, Sanchez-Guijo A, Hartmann MF, Wudy SA, Bernhardt R. 2017. The steroid metabolite 16β-OH-androstenedione generated by CYP21A2 serves as a substrate for CYP19A1. J Steroid Biochem Mol Biol. 167:182–191.
  • Nguyen DP, O'Malley P, Al Hussein Al Awamlh B, Furrer MA, Mongan NP, Robinson BD, Wang GJ, Scherr DS. 2017. Association of aromatase with bladder cancer stage and long-term survival: new insights into the hormonal paradigm in bladder cancer. Clin Genitourinary Cancer. 15:256–262.e251.
  • Niinivehmas S, Postila PA, Rauhamäki S, Manivannan E, Kortet S, Ahinko M, Huuskonen P, Nyberg N, Koskimies P, Lätti S, et al. 2018. Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives. J Enzyme Inhib Med Chem. 33:743–754.
  • Ning B, Dial S, Sun Y, Wang J, Yang J, Guo L. 2008. Systematic and simultaneous gene profiling of 84 drug-metabolizing genes in primary human hepatocytes. J Biomol Screen. 13:194–201.
  • Noda M, Ohno S, Nakajin S. 2007. Mono-(2-ethylhexyl) phthalate (MEHP) induces nuclear receptor 4A subfamily in NCI-H295R cells: a possible mechanism of aromatase suppression by MEHP. Mol Cell Endocrinol. 274:8–18.
  • Numazawa M, Ando M, Watari Y, Tominaga T, Hayata Y, Yoshimura A. 2005. Structure-activity relationships of 2-, 4-, or 6-substituted estrogens as aromatase inhibitors. J Steroid Biochem Mol Biol. 96:51–58.
  • Numazawa M, Mutsumi A, Tachibana M, Yoshimura A. 2003. Kinetic analysis of reversible inhibition of 16α-hydroxyandrostenedione aromatization in human placental microsomes by suicide substrates of androstenedione aromatization. Biol Pharmaceut Bull. 26:890–892.
  • Numazawa M, Shelangouski M, Nagasaka M. 2000. Probing the binding pocket of the active site of aromatase with 6-ether or 6-ester substituted androst-4-ene-3,17-diones and their diene and triene analogs. Steroids. 65:871–882.
  • Numazawa M, Tachibana M, Mutsumi A, Yoshimura A, Osawa Y. 2002. Aromatization of 16α-hydroxyandrostenedione by human placental microsomes: effect of preincubation with suicide substrates of androstenedione aromatization. J Steroid Biochem Mol Biol. 81:165–172.
  • Numazawa M, Yamada K. 1999. Studies of the time-dependent inactivation of aromatase by 4β,5β-epoxy-6-one and 5β,6β-epoxy-4-one steroids under various conditions. Biol Pharm Bull. 22:1207–1211.
  • Numazawa M, Yamaguchi S. 1998. 6-Phenylaliphatic-substituted androst-4-ene-3,17-diones as aromatase inhibitors: structure-activity relationships. J Steroid Biochem Mol Biol. 67:41–48.
  • Numazawa M, Yamaguchi S. 1999. Synthesis and structure-activity relationships of 6-phenylaliphatic-substituted C19 steroids having a 1,4-diene, 4,6-diene, or 1,4,6-triene structure as aromatase inhibitors. Steroids. 64:187–196.
  • Numazawa M, Yoshimura A, Oshibe M. 1998. Enzymic aromatization of 6-alkyl-substituted androgens, potent competitive and mechanism-based inhibitors of aromatase. Biochem J. 329:151–156.
  • Odum J, Ashby J. 2002. Detection of aromatase inhibitors in vitro using rat ovary microsomes. Toxicol Lett. 129:119–122.
  • Okada M, Yoden T, Kawaminami E, Shimada Y, Kudoh M, Isomura Y. 1997. Studies on aromatase inhibitors. IV. Synthesis and biological evaluation of N,N-disubstituted-5-aminopyrimidine derivatives. Chem Pharm Bull. 45:1293–1299.
  • Oskarsson A, Ohlsson Andersson A. 2016. Suppressed sex hormone biosynthesis by alkylresorcinols: a possible link to chemoprevention. Nutr Cancer. 68:978–987.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Pino AM, Rodriguez JM, Rios S, Astudillo P, Leiva L, Seitz G, Fernandez M, Rodriguez JP. 2006. Aromatase activity of human mesenchymal stem cells is stimulated by early differentiation, vitamin D and leptin. J Endocrinol. 191:715–725.
  • Pogrmic-Majkic K, Samardzija D, Stojkov-Mimic N, Vukosavljevic J, Trninic-Pjevic A, Kopitovic V, Andric N. 2018. Atrazine suppresses FSH-induced steroidogenesis and LH-dependent expression of ovulatory genes through PDE-cAMP signaling pathway in human cumulus granulosa cells. Mol Cell Endocrinol. 461:79–88.
  • Pokhrel M, Ma E. 2011. Synthesis and screening of aromatase inhibitory activity of substituted C19 steroidal 17-oxime analogs. Molecules. 16:9868–9885.
  • Pu W, Yuan Y, Lu D, Wang X, Liu H, Wang C, Wang F, Zhang G. 2016. 2-Phenylbenzo[b]furans: synthesis and promoting activity on estrogen biosynthesis. Bioorg Med Chem Lett. 26:5497–5500.
  • Punetha A, Shanmugam K, Sundar D. 2011. Insight into the enzyme-inhibitor interactions of the first experimentally determined human aromatase. J Biomol Struct Dyn. 28:759–771.
  • Purohit A, Ghilchik MW, Leese MP, Potter BV, Reed MJ. 2005. Regulation of aromatase activity by cytokines, PGE2 and 2-methoxyoestrone-3-O-sulphamate in fibroblasts derived from normal and malignant breast tissues. J Steroid Biochem Mol Biol. 94:167–172.
  • Raobaikady B, Parsons MF, Reed MJ, Purohit A. 2007. Tibolone and its Δ4,7α-methyl norethisterone metabolite are reversible inhibitors of human aromatase. J Steroid Biochem Mol Biol. 104:154–160.
  • Rice S, Mason HD, Whitehead SA. 2006. Phytoestrogens and their low dose combinations inhibit mRNA expression and activity of aromatase in human granulosa-luteal cells. J Steroid Biochem Mol Biol. 101:216–225.
  • Rice S, Pellatt L, Ramanathan K, Whitehead SA, Mason HD. 2009. Metformin inhibits aromatase via an extracellular signal-regulated kinase-mediated pathway. Endocrinology. 150:4794–4801.
  • Rieke S, Koehn S, Hirsch-Ernst K, Pfeil R, Kneuer C, Marx-Stoelting P. 2014. Combination effects of (tri)azole fungicides on hormone production and xenobiotic metabolism in a human placental cell line. Int J Environ Res Publ Health. 11:9660–9679.
  • Robertson KM, O'Donnell L, Jones ME, Meachem SJ, Boon WC, Fisher CR, Graves KH, McLachlan RI, Simpson ER. 1999. Impairment of spermatogenesis in mice lacking a functional aromatase (cyp19) gene. Proc Natl Acad Sci USA. 96:7986–7991.
  • Rochira V, Zirilli L, Maffei L, Premrou V, Aranda C, Baldi M, Ghigo E, Aimaretti G, Carani C, Lanfranco F. 2010. Tall stature without growth hormone: Four male patients with aromatase deficiency. J Clin Endocrinol Metab. 95:1626–1633.
  • Saarinen N, Joshi SC, Ahotupa M, Li X, Ammala J, Makela S, Santti R. 2001. No evidence for the in vivo activity of aromatase-inhibiting flavonoids. J Steroid Biochem Mol Biol. 78:231–239.
  • Saberi MR, Vinh TK, Yee SW, Griffiths BJ, Evans PJ, Simons C. 2006. Potent CYP19 (aromatase) 1-[(benzofuran-2-yl)(phenylmethyl)pyridine, -imidazole, and -triazole inhibitors: synthesis and biological evaluation. J Med Chem. 49:1016–1022.
  • Sanderson JT, Boerma J, Lansbergen GW, van den Berg M. 2002. Induction and inhibition of aromatase (CYP19) activity by various classes of pesticides in H295R human adrenocortical carcinoma cells. Toxicol Appl Pharmacol. 182:44–54.
  • Sanderson JT, Hordijk J, Denison MS, Springsteel MF, Nantz MH, van den Berg M. 2004. Induction and inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells. Toxicol Sci. 82:70–79.
  • Sanderson JT, Letcher RJ, Heneweer M, Giesy JP, van den Berg M. 2001. Effects of chloro-s-triazine herbicides and metabolites on aromatase activity in various human cell lines and on vitellogenin production in male carp hepatocytes. Environ Health Perspect. 109:1027–1031.
  • Sanderson JT, Seinen W, Giesy JP, van den Berg M. 2000. 2-Chloro-S-triazine herbicides induce aromatase (CYP19) activity in H295R human adrenocortical carcinoma cells: a novel mechanism for estrogenicity? Toxicol Sci. 54:121–127.
  • Sanderson T, Renaud M, Scholten D, Nijmeijer S, van den Berg M, Cowell S, Guns E, Nelson C, Mutarapat T, Ruchirawat S. 2008. Effects of lactone derivatives on aromatase (CYP19) activity in H295R human adrenocortical and (anti)androgenicity in transfected LNCaP human prostate cancer cells. Eur J Pharmacol. 593:92–98.
  • Satoh K, Sakamoto Y, Ogata A, Nagai F, Mikuriya H, Numazawa M, Yamada K, Aoki N. 2002. Inhibition of aromatase activity by green tea extract catechins and their endocrinological effects of oral administration in rats. Food Chem Toxicol. 40:925–933.
  • Schmidt M, Löffler G. 1997. RU486 is a potent inhibitor of aromatase induction in human breast adipose tissue stromal cells. J Steroid Biochem Mol Biol. 60:197–204.
  • Seralini G, Moslemi S. 2001. Aromatase inhibitors: past, present and future. Mol Cell Endocrinol. 178:117–131.
  • Sgrignani J, Bon M, Colombo G, Magistrato A. 2014. Computational approaches elucidate the allosteric mechanism of human aromatase inhibition: a novel possible route to small-molecule regulation of CYP450s activities? J Chem Inform Modeling. 54:2856–2868.
  • Shim KS. 2015. Pubertal growth and epiphyseal fusion. Ann Ped Endocrinol Metab. 20:8–12.
  • Shozu M, Fukami M, Ogata T. 2014. Understanding the pathological manifestations of aromatase excess syndrome: lessons for clinical diagnosis. Expert Rev Endocrinol Metab. 9:397–409.
  • Simon V, Avet C, Grange-Messent V, Wargnier R, Denoyelle C, Pierre A, Dairou J, Dupret JM, Cohen-Tannoudji J. 2017. Carbon black nanoparticles inhibit aromatase expression and estradiol secretion in human granulosa cells through the ERK1/2 pathway. Endocrinology. 158:3200–3211.
  • Simpson ER. 2003. Sources of estrogen and their importance. J Steroid Biochem Mol Biol. 86:225–230.
  • Simpson ER, Clyne C, Rubin G, Boon WC, Robertson K, Britt K, Speed C, Jones M. 2002. Aromatase–a brief overview. Annu Rev Physiol. 64:93–127.
  • Sluijmer AV, Heineman MJ, De Jong FH, Evers JL. 1995. Endocrine activity of the postmenopausal ovary: the effects of pituitary down-regulation and oophorectomy. J Clin Endocrinol Metab. 80:2163–2167.
  • Song R, He Y, Murphy MB, Yeung LW, Yu RM, Lam MH, Lam PK, Hecker M, Giesy JP, Wu RS, et al. 2008. Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line. Chemosphere. 71:1888–1894.
  • Stillman SC, Evans BA, Hughes IA. 1991. Androgen dependent stimulation of aromatase activity in genital skin fibroblasts from normals and patients with androgen insensitivity. Clin Endocrinol. 35:533–538.
  • Su B, Diaz-Cruz ES, Landini S, Brueggemeier RW. 2006. Novel sulfonanilide analogues suppress aromatase expression and activity in breast cancer cells independent of COX-2 inhibition. J Med Chem. 49:1413–1419.
  • Su B, Diaz-Cruz ES, Landini S, Brueggemeier RW. 2008. Suppression of aromatase in human breast cells by a cyclooxygenase-2 inhibitor and its analog involves multiple mechanisms independent of cyclooxygenase-2 inhibition. Steroids. 73:104–111.
  • Su B, Hackett JC, Diaz-Cruz ES, Kim YW, Brueggemeier RW. 2005. Lead optimization of 7-benzyloxy 2-(4´-pyridylmethyl)thio isoflavone aromatase inhibitors. Bioorg Med Chem. 13:6571–6577.
  • Sureram S, Wiyakrutta S, Ngamrojanavanich N, Mahidol C, Ruchirawat S, Kittakoop P. 2012. Depsidones, aromatase inhibitors and radical scavenging agents from the marine-derived fungus Aspergillus unguis CRI282-03. Planta Med. 78:582–588.
  • Takemura Y, Osuga Y, Yoshino O, Hasegawa A, Hirata T, Hirota Y, Nose E, Morimoto C, Harada M, Koga K, et al. 2007. Metformin suppresses interleukin (IL)-1β-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab. 92:3213–3218.
  • Tam TW, Liu R, Arnason JT, Krantis A, Staines WA, Haddad PS, Foster BC. 2009. Actions of ethnobotanically selected Cree anti-diabetic plants on human cytochrome P450 isoforms and flavin-containing monooxygenase 3. J Ethnopharmacol. 126:119–126.
  • Tan T, Wang L, Wang B. 2015. Collagen and prostaglandin E2 regulate aromatase expression through the PI3K/AKT/IKK and the MAP kinase pathways in adipose stromal cells. Mol Med Rep. 12:4766–4772.
  • Trösken ER, Fischer K, Volkel W, Lutz WK. 2006. Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation. Toxicology. 219:33–40.
  • Trösken ER, Scholz K, Lutz RW, Volkel W, Zarn JA, Lutz WK. 2004. Comparative assessment of the inhibition of recombinant human CYP19 (aromatase) by azoles used in agriculture and as drugs for humans. Endocr Res. 30:387–394.
  • van Meeuwen JA, Korthagen N, de Jong PC, Piersma AH, van den Berg M. 2007. (Anti)estrogenic effects of phytochemicals on human primary mammary fibroblasts, MCF-7 cells and their co-culture. Toxicol Appl Pharmacol. 221:372–383.
  • van Meeuwen JA, Nijmeijer S, Mutarapat T, Ruchirawat S, de Jong PC, Piersma AH, van den Berg M. 2008. Aromatase inhibition by synthetic lactones and flavonoids in human placental microsomes and breast fibroblasts–a comparative study. Toxicol Appl Pharmacol. 228:269–276.
  • Vanden Bossche HV, Moereels H, Koymans LM. 1994. Aromatase inhibitors–mechanisms for non-steroidal inhibitors. Breast Cancer Res Treat. 30:43–55.
  • Vinggaard AM, Hnida C, Breinholt V, Larsen JC. 2000. Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro. 14:227–234.
  • Vinh TK, Nicholls PJ, Kirby AJ, Simons C. 2001. Evaluation of 7-hydroxy-flavones as inhibitors of oestrone and oestradiol biosynthesis. J Enz Inhib. 16:417–424.
  • Wang C, Mäkelä T, Hase T, Adlercreutz H, Kurzer MS. 1994. Lignans and flavonoids inhibit aromatase enzyme in human preadipocytes. J Steroid Biochem Mol Biol. 50:205–212.
  • Wang Q, Zhao H, Xiang Q, Ju H, Han SM, Wang LY, Xu B. 2009. Effect of Yikun Neiyi Wan on the expression of aromatase P450, COX-2, and ER related receptor in endometrial cells in vitro from patients with endometriosis. J Trad Chinese Med. 29:296–300.
  • Wang Y, Chan FL, Chen S, Leung LK. 2005. The plant polyphenol butein inhibits testosterone-induced proliferation in breast cancer cells expressing aromatase. Life Sci. 77:39–51.
  • Wang Y, Lee KW, Chan FL, Chen S, Leung LK. 2006. The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells. Toxicol Sci. 92:71–77.
  • Wang Y, Leung LK. 2007. Pharmacological concentration of resveratrol suppresses aromatase in JEG-3 cells. Toxicol Lett. 173:175–180.
  • Watanabe M, Noda M, Nakajin S. 2006. Effect of epidermal growth factor and prostaglandin on the expression of aromatase (CYP19) in human adrenocortical carcinoma cell line NCI-H295R cells. J Endocrinol. 188:59–68.
  • Watanabe M, Ohno S, Nakajin S. 2005. Forskolin and dexamethasone synergistically induce aromatase (CYP19) expression in the human osteoblastic cell line SV-HFO. Eur J Endocrinol. 152:619–624.
  • White EL, Ross LJ, Steele VE, Kelloff GJ, Hill DL. 1999. Screening of potential cancer preventing chemicals as aromatase inhibitors in an in vitro assay. Anticancer Res. 19:1017–1020.
  • Whitehead SA, Lacey M. 2003. Phytoestrogens inhibit aromatase but not 17β-hydroxysteroid dehydrogenase (HSD) type 1 in human granulosa-luteal cells: evidence for FSH induction of 17β-HSD. Hum Reprod. 18(3):487–494.
  • Wit JM, Hero M, Nunez SB. 2011. Aromatase inhibitors in pediatrics. Nat Rev Endocrinol. 8:135–147.
  • Wójtowicz AK, Milewicz T, Gregoraszczuk EL. 2007. DDT and its metabolite DDE alter steroid hormone secretion in human term placental explants by regulation of aromatase activity. Toxicol Lett. 173:24–30.
  • Wu S, Ye J, Wang Z, Lin SX, Lu M, Liang Y, Zhu X, Olumi AF, Zhong WD, Wu CL. 2018. Expression of aromatase in tumor related stroma is associated with human bladder cancer progression. Cancer Biol Ther. 19:175–180.
  • Yahiaoui S, Pouget C, Fagnere C, Champavier Y, Habrioux G, Chulia AJ. 2004. Synthesis and evaluation of 4-triazolylflavans as new aromatase inhibitors. Bioorg Med Chem Lett. 14:5215–5218.
  • Yanase T, Mu YM, Nishi Y, Goto K, Nomura M, Okabe T, Takayanagi R, Nawata H. 2001. Regulation of aromatase by nuclear receptors. J Steroid Biochem Mol Biol. 79:187–192.
  • Yanase T, Suzuki S, Goto K, Nomura M, Okabe T, Takayanagi R, Nawata H. 2003. Aromatase in bone: Roles of vitamin D3 and androgens. J Steroid Biochem Mol Biol. 86:393–397.
  • Yoshimoto FK, Guengerich FP. 2014. Mechanism of the third oxidative step in the conversion of androgens to estrogens by cytochrome P450 19A1 steroid aromatase. J Am Chem Soc. 136:15016–15025.
  • Yumoto T, Ando K, Okamoto K, Okamoto S, Yoshida Y. 1976. Studies on immunoblastic lymphadenopathy in the New Zealand Black strain mice (author's transl). Nihon Ketsueki Gakkai Zasshi. 39:170–181. Japanese.
  • Zarn JA, Bruschweiler BJ, Schlatter JR. 2003. Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14α-demethylase and aromatase. Environ Health Perspect. 111:255–261.
  • Zhang Y, He Y, Liu C, Liu C, Li S. 2018. In vitro screening and isolation of human aromatase inhibitors from Cicer arietinum by a novel continuous online method combining chromatographic techniques. J Sep Sci. 41:483–492.
  • Zhao Y, Nichols JE, Valdez R, Mendelson CR, Simpson ER. 1996. Tumor necrosis factor-alpha stimulates aromatase gene expression in human adipose stromal cells through use of an activating protein-1 binding site upstream of promoter 1.4. Mol Endocrinol. 10:1350–1357.
  • Zharikova OL, Deshmukh SV, Kumar M, Vargas R, Nanovskaya TN, Hankins GD, Ahmed MS. 2007. The effect of opiates on the activity of human placental aromatase/CYP19. Biochem Pharmacol. 73:279–286.
  • Zharikova OL, Deshmukh SV, Nanovskaya TN, Hankins GD, Ahmed MS. 2006. The effect of methadone and buprenorphine on human placental aromatase. Biochem Pharmacol. 71:1255–1264.
  • Zhong S, Ye WP, Xu PP, Feng E, Li H, Lin SH, Liu JY, Ma C, Lin YC. 2010. Aromatase expression in leptin-pretreated human breast pre-adipocytes is enhanced by zeranol and suppressed by (-)-gossypol. Anticancer Res. 30:5077–5084.
  • Zhou DJ, Pompon D, Chen SA. 1990. Stable expression of human aromatase complementary DNA in mammalian cells: a useful system for aromatase inhibitor screening. Cancer Res. 50:6949–6954.
  • Zhu SJ, Li Y, Li H, Wang YL, Xiao ZJ, Vihko P, Piao YS. 2002. Retinoic acids promote the action of aromatase and 17β-hydroxysteroid dehydrogenase type 1 on the biosynthesis of 17β-estradiol in placental cells. J Endocrinol. 172:31–43.

References

  • Asif AR, Ljubojevic M, Sabolic I, Shnitsar V, Metten M, Anzai N, Muller GA, Burckhardt G, Hagos Y. 2006. Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells. Am J Physiol Endocrinol Metab. 291:E1351–1359.
  • Auchus RJ, Sampath Kumar A, Andrew Boswell C, Gupta MK, Bruce K, Rath NP, Covey DF. 2003. The enantiomer of progesterone (ent-progesterone) is a competitive inhibitor of human cytochromes P450c17 and P450c21. Arch Biochem Biophys. 409:134–144.
  • Ayub M, Levell MJ. 1990. The inhibition of human prostatic aromatase activity by imidazole drugs including ketoconazole and 4-hydroxyandrostenedione. Biochem Pharmacol. 40:1569–1575.
  • Blaha L, Hilscherova K, Mazurova E, Hecker M, Jones PD, Newsted JL, Bradley PW, Gracia T, Duris Z, Horka I, et al. 2006. Alteration of steroidogenesis in H295R cells by organic sediment contaminants and relationships to other endocrine disrupting effects. Environ Int. 32:749–757.
  • Coulter CL, Jaffe RB. 1998. Functional maturation of the primate fetal adrenal in vivo: 3. Specific zonal localization and developmental regulation of CYP21A2 (P450c21) and CYP11B1/CYP11B2 (P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis. Endocrinology. 139:5144–5150.
  • Ding L, Murphy MB, He Y, Xu Y, Yeung LW, Wang J, Zhou B, Lam PK, Wu RS, Giesy JP. 2007. Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line. Environ Toxicol Chem. 26:764–772.
  • Dowie LJ, Smith JE, MacGilchrist AJ, Fraser R, Honour JW, Reid JL, Kenyon CJ. 1988. In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis. Eur J Clin Pharmacol. 35:625–629.
  • Dragan CA, Hartmann RW, Bureik M. 2006. A fission yeast-based test system for the determination of IC50 values of anti-prostate tumor drugs acting on CYP21. J Enzyme Inhib Med Chem. 21:547–556.
  • Haider S, Islam B, D'Atri V, Sgobba M, Poojari C, Sun L, Yuen T, Zaidi M, New MI. 2013. Structure-phenotype correlations of human CYP21A2 mutations in congenital adrenal hyperplasia. Proc Natl Acad Sci USA. 110:2605–2610.
  • Hasegawa E, Nakagawa S, Sato M, Tachikawa E, Yamato S. 2013. Effect of polyphenols on production of steroid hormones from human adrenocortical NCI-H295R cells. Biol Pharmaceut Bull. 36:228–237.
  • Johansson MK, Sanderson JT, Lund BO. 2002. Effects of 3-MeSO2-DDE and some CYP inhibitors on glucocorticoid steroidogenesis in the H295R human adrenocortical carcinoma cell line. Toxicol In Vitro. 16:113–121.
  • Lin CJ, Cheng LC, Lin TC, Wang CJ, Li LA. 2014. Assessment of the potential of polyphenols as a CYP17 inhibitor free of adverse corticosteroid elevation. Biochem Pharmacol. 90:288–296.
  • Lin CW, Chang YH, Pu HF. 2012. Mitotane exhibits dual effects on steroidogenic enzymes gene transcription under basal and cAMP-stimulating microenvironments in NCI-H295 cells. Toxicology. 298:14–23.
  • Lundqvist J, Norlin M, Wikvall K. 2010. 1α,25-Dihydroxyvitamin D3 affects hormone production and expression of steroidogenic enzymes in human adrenocortical NCI-H295R cells. Biochim Biophys Acta. 1801:1056–1062.
  • Malikova J, Brixius-Anderko S, Udhanea SS, Parween S, Dick B, Bernhardt R, Pandey AV. 2017. CYP17A1 inhibitor abiraterone, an anti-prostate cancer drug, also inhibits the 21-hydroxylase activity of CYP21A2. J Steroid Biochem Mol Biol. 174:192–200.
  • Ohlsson A, Ulleras E, Oskarsson A. 2009. A biphasic effect of the fungicide prochloraz on aldosterone, but not cortisol, secretion in human adrenal H295R cells–underlying mechanisms. Toxicol Lett. 191:174–180.
  • Oskarsson A, Ohlsson Andersson A. 2016. Suppressed sex hormone biosynthesis by alkylresorcinols: a possible link to chemoprevention. Nutr Cancer. 68:978–987.
  • Pallan PS, Lei L, Wang C, Waterman MR, Guengerich FP, Egli M. 2015. Research resource: correlating human cytochrome P450 21A2 crystal structure and phenotypes of mutations in congenital adrenal hyperplasia. Mol Endocrinol. 29:1375–1384.
  • Pallan PS, Wang C, Lei L, Yoshimoto FK, Auchus RJ, Waterman MR, Guengerich FP, Egli M. 2015. Human cytochrome P450 21A2, the major steroid 21-hydroxylase: structure of the enzyme•progesterone substrate complex and rate-limiting C-H bond cleavage. J Biol Chem. 290:13128–13143.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Parr MK, Zöllner A, Fussholler G, Opfermann G, Schlörer N, Zorio M, Bureik M, Schanzer W. 2012. Unexpected contribution of cytochrome P450 enzymes CYP11B2 and CYP21, as well as CYP3A4 in xenobiotic androgen elimination–insights from metandienone metabolism. Toxicol Lett. 213:381–391.
  • Schroeder RL, Tram P, Liu J, Foroozesh M, Sridhar J. 2016. Novel functionalized 5-(phenoxymethyl)-1,3-dioxane analogs exhibiting cytochrome P450 inhibition: a patent evaluation WO2015048311 (A1). Exp Opin Ther Pat. 26:139–147.
  • Song R, He Y, Murphy MB, Yeung LW, Yu RM, Lam MH, Lam PK, Hecker M, Giesy JP, Wu RS, et al. 2008. Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line. Chemosphere. 71:1888–1894.
  • Wang C, Pallan PS, Zhang W, Lei L, Yoshimoto FK, Waterman MR, Egli M, Guengerich FP. 2017. Functional analysis of human cytochrome P450 21A2 variants involved in congenital adrenal hyperplasia. J Biol Chem. 292:10767–10778.
  • Wenzel J, Grabinski N, Knopp CA, Dendorfer A, Ramanjaneya M, Randeva HS, Ehrhart-Bornstein M, Dominiak P, Johren O. 2009. Hypocretin/orexin increases the expression of steroidogenic enzymes in human adrenocortical NCI H295R cells. Am J Physiol Regl Integrative Comp Physiol. 297:R1601–1609.
  • Yoshimoto FK, Desilets MC, Auchus RJ. 2012. Synthesis of halogenated pregnanes, mechanistic probes of steroid hydroxylases CYP17A1 and CYP21A2. J Steroid Biochem Mol Biol. 128:38–50.
  • Zhao B, Lei L, Kagawa N, Sundaramoorthy M, Banerjee S, Nagy LD, Guengerich FP, Waterman MR. 2012. Three-dimensional structure of steroid 21-hydroxylase (cytochrome P450 21A2) with two substrates reveals locations of disease-associated variants. J Biol Chem. 287:10613–10622.
  • Zöllner A, Parr MK, Dragan CA, Dras S, Schlorer N, Peters FT, Maurer HH, Schanzer W, Bureik M. 2010. CYP21-catalyzed production of the long-term urinary metandienone metabolite 17β-hydroxymethyl-17α-methyl-18-norandrosta-1,4,13-trien-3-one: a contribution to the fight against doping. Biol Chem. 391:119–127.

References

  • Abe D, Sakaki T, Kusudo T, Kittaka A, Saito N, Suhara Y, Fujishima T, Takayama H, Hamamoto H, Kamakura M, et al. 2005. Metabolism of 2α-propoxy-1α,25-dihydroxyvitamin D3 and 2α-(3-hydroxypropoxy)-1α,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1. Drug Metab Dispos. 33:778–784.
  • Acimovic J, Goyal S, Kosir R, Golicnik M, Perse M, Belic A, Urlep Z, Guengerich FP, Rozman D. 2016. Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis. Sci Rep. 6:28462.
  • Alfaqih MA, Nelson ER, Liu W, Safi R, Jasper JS, Macias E, Geradts J, Thompson JW, Dubois LG, Freeman MR, et al. 2017. CYP27A1 loss dysregulates cholesterol homeostasis in prostate cancer. Cancer Res. 77:1662–1673.
  • An S, Jang YS, Park JS, Kwon BM, Paik YK, Jeong TS. 2008. Inhibition of acyl-coenzyme A:cholesterol acyltransferase stimulates cholesterol efflux from macrophages and stimulates farnesoid X receptor in hepatocytes. Exp Mol Med. 40:407–417.
  • Araya Z, Tang W, Wikvall K. 2003. Hormonal regulation of the human sterol 27-hydroxylase gene CYP27A1. Biochem J. 372:529–534.
  • Björkhem I. 2013. Cerebrotendinous xanthomatosis. Curr Opin Lipidol. 24:283–287.
  • Burkard I, von Eckardstein A, Waeber G, Vollenweider P, Rentsch KM. 2007. Lipoprotein distribution and biological variation of 24S- and 27-hydroxycholesterol in healthy volunteers. Atherosclerosis. 194:71–78.
  • Chen W, Chiang JY. 2003. Regulation of human sterol 27-hydroxylase gene (CYP27A1) by bile acids and hepatocyte nuclear factor 4α (HNF4α). Gene. 313:71–82.
  • Diesing D, Cordes T, Fischer D, Diedrich K, Friedrich M. 2006. Vitamin D–metabolism in the human breast cancer cell line MCF-7. Anticancer Res. 26:2755–2759.
  • DuSell CD, Nelson ER, Wang X, Abdo J, Modder UI, Umetani M, Gesty-Palmer D, Javitt NB, Khosla S, McDonnell DP. 2010. The endogenous selective estrogen receptor modulator 27-hydroxycholesterol is a negative regulator of bone homeostasis. Endocrinology. 151:3675–3685.
  • Ellis E, Axelson M, Abrahamsson A, Eggertsen G, Thorne A, Nowak G, Ericzon BG, Björkhem I, Einarsson C. 2003. Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor. Hepatology. 38:930–938.
  • Ellis EC. 2006. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes. World J Gastroenterol. 12:4640–4645.
  • Federspiel JD, Codreanu SG, Goyal S, Albertolle ME, Lowe E, Teague J, Wong H, Guengerich FP, Liebler DC. 2016. Specificity of protein covalent modification by the electrophilic proteasome inhibitor carfilzomib in human cells. Mol Cell Proteomics. 15:3233–3242.
  • Gueguen Y, Ferrari L, Souidi M, Batt AM, Lutton C, Siest G, Visvikis S. 2007. Compared effect of immunosuppressive drugs cyclosporine A and rapamycin on cholesterol homeostasis key enzymes CYP27A1 and HMG-CoA reductase. Basic Clin Pharmacol Toxicol. 100:392–397.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Honda A, Ikegami T, Nakamuta M, Miyazaki T, Iwamoto J, Hirayama T, Saito Y, Takikawa H, Imawari M, Matsuzaki Y. 2013. Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid. Hepatology. 57:1931–1941.
  • Kalaany NY, Mangelsdorf DJ. 2006. LXRS and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol. 68:159–191.
  • Kimbung S, Chang CY, Bendahl PO, Dubois L, Thompson JW, McDonnell DP, Borgquist S. 2017. Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer. Endocr Relat Cancer. 24:339–349.
  • Lam M, Mast N, Pikuleva IA. 2018. Drugs and scaffold that inhibit cytochrome P450 27A1 in vitro and in vivo. Mol Pharmacol. 93:101–108.
  • Li T, Chen W, Chiang JY. 2007. PXR induces CYP27A1 and regulates cholesterol metabolism in the intestine. J Lipid Res. 48:373–384.
  • Llaverias G, Rebollo A, Pou J, Vazquez-Carrera M, Sanchez RM, Laguna JC, Alegret M. 2006. Effects of rosiglitazone and atorvastatin on the expression of genes that control cholesterol homeostasis in differentiating monocytes. Biochem Pharmacol. 71:605–614.
  • Lloyd-Jones DM, Walsh JA, Prineas RJ, Ning H, Liu K, Daviglus ML, Shea S, Detrano RC, Tandri H, Greenland P. 2009. Association of electrocardiographic abnormalities with coronary artery calcium and carotid artery intima-media thickness in individuals without clinical coronary heart disease (from the Multi-Ethnic Study of Atherosclerosis [MESA]). Am J Cardiol. 104:1086–1091.
  • Lutz SZ, Hennenlotter J, Scharpf MO, Sailer C, Fritsche L, Schmid V, Kantartzis K, Wagner R, Lehmann R, Berti L, et al. 2018. Androgen receptor overexpression in prostate cancer in type 2 diabetes. Mol Metab. 8:158–166.
  • Lyons MA, Brown AJ. 2001. Metabolism of an oxysterol, 7-ketocholesterol, by sterol 27-hydroxylase in HepG2 cells. Lipids. 36:701–711.
  • Mast N, Lin JB, Pikuleva IA. 2015. Marketed drugs can inhibit cytochrome P450 27A1, a potential new target for breast cancer adjuvant therapy. Mol Pharmacol. 88:428–436
  • Masumoto O, Ohyama Y, Okuda K. 1988. Purification and characterization of vitamin D 25-hydroxylase from rat liver mitochondria. J Biol Chem. 263:14256–14260.
  • Meaney S, Bodin K, Diczfalusy U, Björkhem I. 2002. On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation: critical importance of the position of the oxygen function. J Lipid Res. 43:2130–2135.
  • Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, Carver NJ, Pillai RV, Sullivan PM, Sondhi V, et al. 2013. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 342:1094–1098.
  • Nguyen LB, Shefer S, Salen G, Tint SG, Batta AK. 1998. Competitive inhibition of hepatic sterol 27-hydroxylase by sitosterol: decreased activity in sitosterolemia. Proc Assoc Am Physicians. 110:32–39.
  • Norlin M, von Bahr S, Björkhem I, Wikvall K. 2003. On the substrate specificity of human CYP27A1: implications for bile acid and cholestanol formation. J Lipid Res. 44:1515–1522.
  • Norlin M, Wikvall K. 2007. Enzymes in the conversion of cholesterol into bile acids. Curr Mol Med. 7:199–218.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Pettersson H, Norlin M, Andersson U, Pikuleva I, Björkhem I, Misharin AY, Wikvall K. 2008. Metabolism of a novel side chain modified Δ8(14)-15-ketosterol, a potential cholesterol lowering drug: 28-hydroxylation by CYP27A1. Biochim Biophys Acta. 1781:383–390.
  • Pikuleva IA, Mast N, Liao WL, Turko IV. 2008. Studies of membrane topology of mitochondrial cholesterol hydroxylases CYPs 27A1 and 11A1. Lipids. 43:1127–1132.
  • Quinn CM, Jessup W, Wong J, Kritharides L, Brown AJ. 2005. Expression and regulation of sterol 27-hydroxylase (CYP27A1) in human macrophages: a role for RXR and PPARγ ligands. Biochem J. 385:823–830.
  • Sakaki T, Kagawa N, Yamamoto K, Inouye K. 2005. Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 10:119–134.
  • Schuster I, Egger H, Herzig G, Reddy GS, Schmid JA, Schussler M, Vorisek G. 2006. Selective inhibitors of vitamin D metabolism–new concepts and perspectives. Anticancer Res. 26:2653–2668.
  • Sharanek A, Burban A, Humbert L, Bachour-El Azzi P, Felix-Gomes N, Rainteau D, Guillouzo A. 2015. Cellular accumulation and toxic effects of bile acids in cyclosporine A-treated HepaRG hepatocytes. Toxicol Sci. 147:573–587.
  • Szanto A, Benko S, Szatmari I, Balint BL, Furtos I, Ruhl R, Molnar S, Csiba L, Garuti R, Calandra S, et al. 2004. Transcriptional regulation of human CYP27 integrates retinoid, peroxisome proliferator-activated receptor, and liver X receptor signaling in macrophages. Mol Cell Biol. 24:8154–8166.
  • Taban IM, Zhu J, DeLuca HF, Simons C. 2017. Analysis of the binding sites of vitamin D 1α-hydroxylase (CYP27B1) and vitamin D 24-hydroxylase (CYP24A1) for the design of selective CYP24A1 inhibitors: homology modelling, molecular dynamics simulations and identification of key binding requirements. Bioorg Med Chem. 25:5629–5636.
  • Tang W, Norlin M, Wikvall K. 2007. Regulation of human CYP27A1 by estrogens and androgens in HepG2 and prostate cells. Arch Biochem Biophys. 462:13–20.
  • Tieu EW, Li W, Chen J, Baldisseri DM, Slominski AT, Tuckey RC. 2012. Metabolism of cholesterol, vitamin D3 and 20-hydroxyvitamin D3 incorporated into phospholipid vesicles by human CYP27A1. J Steroid Biochem Mol Biol. 129:163–171.
  • Tokar EJ, Webber MM. 2005. Cholecalciferol (vitamin D3) inhibits growth and invasion by up-regulating nuclear receptors and 25-hydroxylase (CYP27A1) in human prostate cancer cells. Clin Exp Metastasis. 22:275–284.
  • Umetani M, Domoto H, Gormley AK, Yuhanna IS, Cummins CL, Javitt NB, Korach KS, Shaul PW, Mangelsdorf DJ. 2007. 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med. 13:1185–1192.
  • Umetani M, Ghosh P, Ishikawa T, Umetani J, Ahmed M, Mineo C, Shaul PW. 2014. The cholesterol metabolite 27-hydroxycholesterol promotes atherosclerosis via proinflammatory processes mediated by estrogen receptor α. Cell Metab. 20:172–182.
  • Umetani M, Shaul PW. 2011. 27-Hydroxycholesterol: the first identified endogenous SERM. Trends Endocrinol Metab. 22:130–135.
  • van Lier JE, Mast N, Pikuleva IA. 2015. Cholesterol hydroperoxides as substrates for cholesterol-metabolizing cytochrome P450 enzymes and alternative sources of 25-hydroxycholesterol and other oxysterols. Angew Chem Int Ed. 54:11138–11142.
  • Wikvall K. 1984. Hydroxylations in biosynthesis of bile acids. Isolation of a cytochrome P-450 from rabbit liver mitochondria catalyzing 26-hydroxylation of C27-steroids. J Biol Chem. 259:3800–3804.
  • Xu Y, Hutchison SM, Hernandez-Ledezma JJ, Bogan RL. 2018. Increased 27-hydroxycholesterol production during luteolysis may mediate the progressive decline in progesterone secretion. Mol Human Reprod. 24:2–13.
  • Yin K, You Y, Swier V, Tang L, Radwan MM, Pandya AN, Agrawal DK. 2015. Vitamin D protects against atherosclerosis via regulation of cholesterol efflux and macrophage polarization in hypercholesterolemic swine. Arterioscler Thromb Vasc Biol. 35:2432–2442.

References

  • Li-Hawkins J, Lund EG, Bronson AD, Russell DW. 2000. Expression cloning of an oxysterol 7α-hydroxylase selective for 24-hydroxycholesterol. J Biol Chem. 275:16543–16549.
  • Li-Hawkins J, Lund EG, Turley SD, Russell DW. 2000. Disruption of the oxysterol 7α-hydroxylase gene in mice. J Biol Chem. 275:16536–16542.
  • Oscarson M, Zanger UM, Rifki OF, Klein K, Eichelbaum M, Meyer UA. 2006. Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther. 80:440–456.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Sumantran VN, Mishra P, Bera R, Sudhakar N. 2016. Microarray analysis of differentially-expressed genes encoding CYP450 and Phase II drug metabolizing enzymes in psoriasis and melanoma. Pharmaceutics. 8. DOI:10.3390/pharmaceutics8010004

References

  • Acimovic J, Goyal S, Kosir R, Golicnik M, Perse M, Belic A, Urlep Z, Guengerich FP, Rozman D. 2016. Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis. Sci Rep. 6:28462.
  • Anderson KW, Mast N, Hudgens JW, Lin JB, Turko IV, Pikuleva IA. 2016. Mapping of the allosteric site in cholesterol hydroxylase CYP46A1 for efavirenz, a drug that stimulates enzyme activity. J Biol Chem. 291:11876–11886.
  • Björkhem I, Lutjohann D, Diczfalusy U, Stahle L, Ahlborg G, Wahren J. 1998. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res. 39:1594–1600.
  • Goyal S, Xiao Y, Porter NA, Xu L, Guengerich FP. 2014. Oxidation of 7-dehydrocholesterol and desmosterol by human cytochrome P450 46A1. J Lipid Res. 55:1933–1943.
  • Halford RW, Russell DW. 2009. Reduction of cholesterol synthesis in the mouse brain does not affect amyloid formation in Alzheimer's disease, but does extend lifespan. Proc Natl Acad Sci USA. 106:3502–3506.
  • Hudry E, Van Dam D, Kulik W, De Deyn PP, Stet FS, Ahouansou O, Benraiss A, Delacourte A, Bougneres P, Aubourg P, et al. 2010. Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer's disease. Mol Ther. 18:44–53.
  • Kotti TJ, Ramirez DM, Pfeiffer BE, Huber KM, Russell DW. 2006. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Proc Natl Acad Sci USA. 103:3869–3874.
  • Liao WL, Dodder NG, Mast N, Pikuleva IA, Turko IV. 2009. Steroid and protein ligand binding to cytochrome P450 46A1 as assessed by hydrogen-deuterium exchange and mass spectrometry. Biochemistry. 48:4150–4158.
  • Lund EG, Guileyardo JM, Russell DW. 1999. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci USA. 96:7238–7243.
  • Lutjohann D, Breuer O, Ahlborg G, Nennesmo I, Siden A, Diczfalusy U, Björkhem I. 1996. Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci USA. 93:9799–9804.
  • Mast N, Anderson KW, Johnson KM, Phan TTN, Guengerich FP, Pikuleva IA. 2017. In vitro cytochrome P450 46A1 (CYP46A1) activation by neuroactive compounds. J Biol Chem. 292:12934–12946.
  • Mast N, Charvet C, Pikuleva IA, Stout CD. 2010. Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain. J Biol Chem. 285:31783–31795.
  • Mast N, Li Y, Linger M, Clark M, Wiseman J, Pikuleva IA. 2014. Pharmacologic stimulation of cytochrome P450 46A1 and cerebral cholesterol turnover in mice. J Biol Chem. 289:3529–3538.
  • Mast N, Linger M, Clark M, Wiseman J, Stout CD, Pikuleva IA. 2012. In silico and intuitive predictions of CYP46A1 inhibition by marketed drugs with subsequent enzyme crystallization in complex with fluvoxamine. Mol Pharmacol. 82:824–834.
  • Mast N, Norcross R, Andersson U, Shou M, Nakayama K, Björkhem I, Pikuleva IA. 2003. Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry. 42:14284–14292.
  • Mast N, White MA, Björkhem I, Johnson EF, Stout CD, Pikuleva IA. 2008. Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc Natl Acad Sci USA. 105:9546–9551.
  • Mast N, Zheng W, Stout CD, Pikuleva IA. 2013. Antifungal azoles: Structural insights into undesired tight binding to cholesterol-metabolizing CYP46A1. Mol Pharmacol. 84:86–94.
  • Meaney S, Bodin K, Diczfalusy U, Björkhem I. 2002. On the rate of translocation in vitro and kinetics in vivo of the major oxysterols in human circulation: critical importance of the position of the oxygen function. J Lipid Res. 43:2130–2135.
  • Nunes MJ, Moutinho M, Milagre I, Gama MJ, Rodrigues E. 2012. Okadaic acid inhibits the trichostatin A-mediated increase of human CYP46A1 neuronal expression in a ERK1/2-Sp3-dependent pathway. J Lipid Res. 53:1910–1919.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Russell DW, Halford RW, Ramirez DM, Shah R, Kotti T. 2009. Cholesterol 24-hydroxylase: an enzyme of cholesterol turnover in the brain. Annu Rev Biochem. 78:1017–1040.
  • Shafaati M, Mast N, Beck O, Nayef R, Heo GY, Björkhem-Bergman L, Lutjohann D, Björkhem I, Pikuleva IA. 2010. The antifungal drug voriconazole is an efficient inhibitor of brain cholesterol 24S-hydroxylase in vitro and in vivo. J Lipid Res. 51:318–323.
  • Testa G, Staurenghi E, Zerbinati C, Gargiulo S, Iuliano L, Giaccone G, Fanto F, Poli G, Leonarduzzi G, Gamba P. 2016. Changes in brain oxysterols at different stages of Alzheimer's disease: their involvement in neuroinflammation. Redox Biol. 10:24–33.

References

  • Arlt W. 2007. P450 oxidoreductase deficiency and Antley–Bixler syndrome. Rev Endocr Metab Disord. 8:301–307.
  • Burton PM, Swinney DC, Heller R, Dunlap B, Chiou M, Malonzo E, Haller J, Walker KA, Salari A, Murakami S, et al. 1995. Azalanstat (RS-21607), a lanosterol 14α-demethylase inhibitor with cholesterol-lowering activity. Biochem Pharmacol. 50:529–544.
  • Cotman M, Rozma D, Banek L, Jezek D. 2001. Localisation of lanosterol 14α-demethylase in round and elongated spermatids of the mouse testis: an immunoelectron microscopic and stereological study. Pflugers Arch. 442(Suppl 1):R167–168.
  • Fischer RT, Trzaskos JM, Magolda RL, Ko SS, Brosz CS, Larsen B. 1991. Lanosterol 14α-methyl demethylase: isolation and characterization of the third metabolically generated oxidative demethylation intermediate. J Biol Chem. 266:6124–6132.
  • Frye LL, Leonard DA. 1999. Lanosterol analogs: dual-action inhibitors of cholesterol biosynthesis. Crit Rev Biochem Mol Biol. 34:123–140.
  • Guengerich FP. 2017. Intersection of the roles of cytochrome P450 enzymes with xenobiotic and endogenous substrates: relevance to toxicity and drug interactions. Chem Res Toxicol. 30:2–12.
  • Guengerich FP, Yoshimoto FK. 2018. Formation and cleavage of C-C bonds by enzymatic oxidation reactions. Chem Rev. 118:6573–6655.
  • Hargrove TY, Friggeri L, Wawrzak Z, Qi A, Hoekstra WJ, Schotzinger RJ, York JD, Guengerich FP, Lepesheva GI. 2017. Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis. J Biol Chem. 292:6728–6743.
  • Hargrove TY, Friggeri L, Wawrzak Z, Sivakumaran S, Yazlovitskaya EM, Hiebert SW, Guengerich FP, Waterman MR, Lepesheva GI. 2016. Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design. J Lipid Res. 57:1552–1563.
  • Hargrove TY, Wawrzak Z, Lamb DC, Guengerich FP, Lepesheva GI. 2015. Structure-functional characterization of cytochrome P450 sterol 14α-demethylase (CYP51B) from Aspergillus fumigatus and molecular basis for the development of antifungal drugs. J Biol Chem. 290:23916–23934.
  • Hargrove TY, Wawrzak Z, Liu J, Waterman MR, Nes WD, Lepesheva GI. 2012. Structural complex of sterol 14α-demethylase (CYP51) with 14α-methylenecyclopropyl-Δ7-24,25-dihydrolanosterol. J Lipid Res. 53:311–320.
  • Harwood HJ, Jr., Petras SF, Hoover DJ, Mankowski DC, Soliman VF, Sugarman ED, Hulin B, Kwon Y, Gibbs EM, Mayne JT, et al. 2005. Dual-action hypoglycemic and hypocholesterolemic agents that inhibit glycogen phosphorylase and lanosterol demethylase. J Lipid Res. 46:547–563.
  • Kaluzhsiy LA, Gnedenko OV, Gilep AA, Strushkevich NV, Shkel TV, Chernovetsky MA, Ivanov AS, Lisitsa AV, Usanov AS, Stonik VA, et al. 2014. The screening of the inhibitors of the human cytochrome P450(51) (CYP51A1): the plant and animal structural lanosterol's analogs. Biomed Khim. 60:528–537. Russian.
  • Keber R, Motaln H, Wagner KD, Debeljak N, Rassoulzadegan M, Acimovic J, Rozman D, Horvat S. 2011. Mouse knockout of the cholesterogenic cytochrome P450 lanosterol 14α-demethylase (Cyp51) resembles Antley-Bixler syndrome. J Biol Chem. 286:29086–29097.
  • Krone N, Dhir V, Ivison HE, Arlt W. 2007. Congenital adrenal hyperplasia and P450 oxidoreductase deficiency. Clin Endocrinol. 66:162–172.
  • Lamb DC, Kelly DE, Kelly SL. 1998. Molecular diversity of sterol 14α-demethylase substrates in plants, fungi and humans. FEBS Lett. 425:263–265.
  • Lepesheva GI, Park HW, Hargrove TY, Vanhollebeke B, Wawrzak Z, Harp JM, Sundaramoorthy M, Nes WD, Pays E, Chaudhuri M, et al. 2010. Crystal structures of Trypanosoma brucei sterol 14α-demethylase and implications for selective treatment of human infections. J Biol Chem. 285:1773–1780.
  • Lepesheva GI, Waterman MR. 2007. Sterol 14α-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms. Biochim Biophys Acta. 1770:467–477.
  • Matsuura K, Yoshioka S, Tosha T, Hori H, Ishimori K, Kitagawa T, Morishima I, Kagawa N, Waterman MR. 2005. Structural diversities of active site in clinical azole-bound forms between sterol 14α-demethylases (CYP51s) from human and Mycobacterium tuberculosis. J Biol Chem. 280:9088–9096.
  • Mayer RJ, Adams JL, Bossard MJ, Berkhout TA. 1991. Effects of a novel lanosterol 14α-demethylase inhibitor on the regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in Hep G2 cells. J Biol Chem. 266:20070–20078.
  • Nakamura T, Iwase A, Bayasula B, Nagatomo Y, Kondo M, Nakahara T, Takikawa S, Goto M, Kotani T, Kiyono T, et al. 2015. CYP51A1 induced by growth differentiation factor 9 and follicle-stimulating hormone in granulosa cells is a possible predictor for unfertilization. Reprod Sci. 22:377–384.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Pont A, Williams PL, Loose DS, Feldman D, Reitz RE, Bochra C, Stevens DA. 1982. Ketoconazole blocks adrenal steroid synthesis. Ann Int Med. 97:370–372.
  • Rozman D, Cotman M, Frangez R. 2002. Lanosterol 14α-demethylase and MAS sterols in mammalian gametogenesis. Mol Cell Endocrinol. 187:179–187.
  • Rozman D, Waterman MR. 1998. Lanosterol 14α-demethylase (CYP51) and spermatogenesis. Drug Metab Dispos. 26:1199–1201.
  • Schuster I, Bernhardt R. 2007. Inhibition of cytochromes P450: existing and new promising therapeutic targets. Drug Metab Rev. 39:481–499.
  • Shyadehi AZ, Lamb DC, Kelly SL, Kelly DE, Schunck WH, Wright JN, Corina D, Akhtar M. 1996. Mechanism of the acyl-carbon bond cleavage reaction catalyzed by recombinant sterol 14α-demethylase of Candida albicans (other names are: lanosterol 14α-demethylase, P-45014DM, and CYP51). J Biol Chem. 271:12445–12450.
  • Stromstedt M, Rozman D, Waterman MR. 1996. The ubiquitously expressed human CYP51 encodes lanosterol 14α-demethylase, a cytochrome P450 whose expression is regulated by oxysterols. Arch Biochem Biophys. 329:73–81.
  • Strushkevich N, Usanov SA, Park HW. 2010. Structural basis of human CYP51 inhibition by antifungal azoles. J Mol Biol. 397:1067–1078.
  • Swinney DC, So OY, Watson DM, Berry PW, Webb AS, Kertesz DJ, Shelton EJ, Burton PM, Walker KA. 1994. Selective inhibition of mammalian lanosterol 14α-demethylase by RS-21607 in vitro and in vivo. Biochemistry. 33:4702–4713.
  • Trösken ER, Adamska M, Arand M, Zarn JA, Patten C, Volkel W, Lutz WK. 2006. Comparison of lanosterol-14α-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles. Toxicology. 228:24–32.
  • Trösken ER, Straube E, Lutz WK, Volkel W, Patten C. 2004. Quantitation of lanosterol and its major metabolite FF-MAS in an inhibition assay of CYP51 by azoles with atmospheric pressure photoionization based LC-MS/MS. J Am Soc Mass Spectrom. 15:1216–1221.
  • Trzaskos JM. 1995. Oxylanosterols as modifiers of cholesterol biosynthesis. Prog Lipid Res. 34:99–116.
  • Trzaskos JM, Magolda RL, Favata MF, Fischer RT, Johnson PR, Chen HW, Ko SS, Leonard DA, Gaylor JL. 1993. Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase by 15α-fluorolanost-7-en-3β-ol. A mechanism-based inhibitor of cholesterol biosynthesis. J Biol Chem. 268:22591–22599.
  • Yoshimoto FK, Guengerich FP. 2014. Mechanism of the third oxidative step in the conversion of androgens to estrogens by cytochrome P450 19A1 steroid aromatase. J Am Chem Soc. 136:15016–15025.

References

  • Abe D, Sakaki T, Kusudo T, Kittaka A, Saito N, Suhara Y, Fujishima T, Takayama H, Hamamoto H, Kamakura M, et al. 2005. Metabolism of 2α-propoxy-1α,25-dihydroxyvitamin D3 and 2α-(3-hydroxypropoxy)-1α,25-dihydroxyvitamin D3 by human CYP27A1 and CYP24A1. Drug Metab Dispos. 33:778–784.
  • Aboraia AS, Makowski B, Bahja A, Prosser D, Brancale A, Jones G, Simons C. 2010. Synthesis and CYP24A1 inhibitory activity of (E)-2-(2-substituted benzylidene)- and 2-(2-substituted benzyl)-6-methoxy-tetralones. Eur J Med Chem. 45:4427–4434.
  • Akiyoshi-Shibata M, Sakaki T, Ohyama Y, Noshiro M, Okuda K, Yabusaki Y. 1994. Further oxidation of hydroxycalcidiol by calcidiol 24-hydroxylase: A study with the mature enzyme expressed in Escherichia coli. Eur J Biochem. 224:335–343.
  • Amano Y, Cho Y, Matsunawa M, Komiyama K, Makishima M. 2009. Increased nuclear expression and transactivation of vitamin D receptor by the cardiotonic steroid bufalin in human myeloid leukemia cells. J Steroid Biochem Mol Biol. 114:144–151.
  • Anderson MG, Nakane M, Ruan X, Kroeger PE, Wu-Wong JR. 2006. Expression of VDR and CYP24A1 mRNA in human tumors. Cancer Chemother Pharmacol. 57:234–240.
  • Annalora AJ, Goodin DB, Hong WX, Zhang Q, Johnson EF, Stout CD. 2010. Crystal structure of CYP24A1, a mitochondrial cytochrome P450 involved in vitamin D metabolism. J Mol Biol. 396:441–451.
  • Avila E, Diaz L, Barrera D, Halhali A, Mendez I, Gonzalez L, Zuegel U, Steinmeyer A, Larrea F. 2007. Regulation of Vitamin D hydroxylases gene expression by 1,25-dihydroxyvitamin D3 and cyclic AMP in cultured human syncytiotrophoblasts. J Steroid Biochem Mol Biol. 103:90–96.
  • Beckman MJ, Tadikonda P, Werner E, Prahl J, Yamada S, Deluca HF. 1996. Human 25-hydroxyvitamin D3-24-hydroxylase, a multicatalytic enzyme. Biochemistry. 35:8465–8472.
  • Brozyna AA, Jochymski C, Janjetovic Z, Jozwicki W, Tuckey RC, Slominski AT. 2014. CYP24A1 expression inversely correlates with melanoma progression: Clinic-pathological studies. Int J Mol Sci. 15:19000–19017.
  • Bruno RD, Njar VC. 2007. Targeting cytochrome P450 enzymes: A new approach in anti-cancer drug development. Bioorg Med Chem. 15:5047–5060.
  • Choi M, Yamada S, Makishima M. 2011. Dynamic and ligand-selective interactions of vitamin D receptor with retinoid X receptor and cofactors in living cells. Mol Pharmacol. 80:1147–1155.
  • Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS. 2003. HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS. 17:513–520.
  • Farhan H, Cross HS. 2002. Transcriptional inhibition of CYP24 by genistein. Ann NY Acad Sci. 973:459–462.
  • Ferla S, Gomaa MS, Brancale A, Zhu J, Ochalek JT, DeLuca HF, Simons C. 2014. Novel styryl-indoles as small molecule inhibitors of 25-hydroxyvitamin D-24-hydroxylase (CYP24A1): Synthesis and biological evaluation. Eur J Med Chem. 87:39–51.
  • Ge N, Chu XM, Xuan YP, Ren DQ, Wang Y, Ma K, Gao HJ, Jiao WJ. 2017. Associations between abnormal vitamin D metabolism pathway function and non-small cell lung cancer. Oncol Lett. 14:7538–7544.
  • Gao XH, Dwivedi PP, Omdahl JL, Morris HA, May BK. 2004. Calcitonin stimulates expression of the rat 25-hydroxyvitamin D3-24-hydroxylase (CYP24) promoter in HEK-293 cells expressing calcitonin receptor: identification of signaling pathways. J Mol Endocrinol. 32:87–98.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: Structure, Mechanism, and Biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Hamamoto H, Kusudo T, Urushino N, Masuno H, Yamamoto K, Yamada S, Kamakura M, Ohta M, Inouye K, Sakaki T. 2006. Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats. Mol Pharmacol. 70:120–128.
  • Horiuchi N, Saikatsu S, Akeno N, Abe M, Kimura S, Yamada S. 1995. Synthesis of 25-hydroxyvitamin D3-26,23-lactone but not 24,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 in opossum kidney cells treated with 1α,25-dihydroxyvitamin D3. Hormone Metabol Res. 27:83–89.
  • Horvath E, Lakatos P, Balla B, Kosa JP, Tóbiás B, Jozilan H, Borka K, Horváth HC, Kovalszky I, Szalay F. 2012. Marked increase of CYP24A1 mRNA level in hepatocellular carcinoma cell lines following vitamin D administration. Anticancer Res. 32:4791–4796.
  • Ikezoe T, Bandobashi K, Yang Y, Takeuchi S, Sekiguchi N, Sakai S, Koeffler HP, Taguchi H. 2006. HIV-1 protease inhibitor ritonavir potentiates the effect of 1,25-dihydroxyvitamin D3 to induce growth arrest and differentiation of human myeloid leukemia cells via down-regulation of CYP24. Leuk Res. 30:1005–1011.
  • Inouye K, Sakaki T. 2001. Enzymatic studies on the key enzymes of vitamin D metabolism; 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24). Biotechnol Annu Rev. 7:179–194.
  • Ishizawa M, Matsunawa M, Adachi R, Uno S, Ikeda K, Masuno H, Shimizu M, Iwasaki K, Yamada S, Makishima M. 2008. Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia. J Lipid Res. 49:763–772.
  • Jones G, Prosser DE, Kaufmann M. 2012. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): Its important role in the degradation of vitamin D. Arch Biochem Biophys. 523:9–18.
  • Jones G, Prosser DE, Kaufmann M. 2014. Cytochrome P450-mediated metabolism of vitamin D. J Lipid Res. 55:13–31.
  • Kaufmann M, Prosser DE, Jones G. 2011. Bioengineering anabolic vitamin D-25-hydroxylase activity into the human vitamin D catabolic enzyme, cytochrome P450 CYP24A1, by a V391L mutation. J Biol Chem. 286:28729–28737.
  • Kemmis CM, Salvador SM, Smith KM, Welsh J. 2006. Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3. J Nutr. 136:887–892.
  • King AN, Beer DG, Christensen PJ, Simpson RU, Ramnath N. 2010. The vitamin D/CYP24A1 story in cancer. Anticancer Agents Med Chem. 10:213–224.
  • Kósa JP, Horváth P, Wölfling J, Kovács D, Balla B, Mátyus P, Horváth E, Speer G, Takács I, Nagy Z, et al. 2013. CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells. World J Gastroenterol. 19:2621–2628.
  • Kusudo T, Sakaki T, Abe D, Fujishima T, Kittaka A, Takayama H, Hatakeyama S, Ohta M, Inouye K. 2004. Metabolism of A-ring diastereomers of 1α,25-dihydroxyvitamin D3 by CYP24A1. Biochem Biophys Res Commun. 321:774–782.
  • Lechner D, Cross HS. 2003. Phytoestrogens and 17β-estradiol influence vitamin D metabolism and receptor expression-relevance for colon cancer prevention. Recent Results Cancer Res. 164:379–391.
  • Lou YR, Miettinen S, Kagechika H, Gronemeyer H, Tuohimaa P. 2005. Retinoic acid via RARα inhibits the expression of 24-hydroxylase in human prostate stromal cells. Biochem Biophys Res Commun. 338:1973–1981.
  • Lou YR, Nazarova N, Talonpoika R, Tuohimaa P. 2005. 5α-Dihydrotestosterone inhibits 1α,25-dihydroxyvitamin D3-induced expression of CYP24 in human prostate cancer cells. Prostate. 63:222–230.
  • Luo W, Hershberger PA, Trump DL, Johnson CS. 2013. 24-Hydroxylase in cancer: Impact on vitamin D-based anticancer therapeutics. J Steroid Biochem Mol Biol. 136:252–257.
  • Makin G, Lohnes D, Byford V, Ray R, Jones G. 1989. Target cell metabolism of 1,25-dihydroxyvitamin D3 to calcitroic acid. Evidence for a pathway in kidney and bone involving 24-oxidation. Biochem J. 262:173–180.
  • Matsunawa M, Amano Y, Endo K, Uno S, Sakaki T, Yamada S, Makishima M. 2009. The aryl hydrocarbon receptor activator benzo[a]pyrene enhances vitamin D3 catabolism in macrophages. Toxicol Sci. 109:50–58.
  • Muindi JR, Yu WD, Ma Y, Engler KL, Kong RX, Trump DL, Johnson CS. 2010. CYP24A1 inhibition enhances the antitumor activity of calcitriol. Endocrinology 151:4301–4312.
  • Nakano H, Matsunawa M, Yasui A, Adachi R, Kawana K, Shimomura I, Makishima M. 2005. Enhancement of ligand-dependent vitamin D receptor transactivation by the cardiotonic steroid bufalin. Biochem Pharmacol. 70:1479–1486.
  • Norlin M, Lundqvist J, Ellfolk M, Hellstrom Pigg M, Gustafsson J, Wikvall K. 2017. Drug-mediated gene regulation of vitamin D3 metabolism in primary human dermal fibroblasts. Basic Clin Pharmacol Toxicol. 120:59–63.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Pascussi JM, Robert A, Nguyen M, Walrant-Debray O, Garabedian M, Martin P, Pineau T, Saric J, Navarro F, Maurel P, et al. 2005. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 115:177–186.
  • Pedersen JI, Hagenfeldt Y, Björkhem I. 1988. Assay and properties of 25-hydroxyvitamin D3 23-hydroxylase. Evidence that 23,25-dihydroxyvitamin D3 is a major metabolite in 1,25-dihydroxyvitamin D3-treated or fasted guinea pigs. Biochem J. 250:527–532.
  • Petkovich M, Jones G. 2011. CYP24A1 and kidney disease. Curr Opin Nephrol Hypertens. 20:337–344.
  • Posner GH, Crawford KR, Yang HW, Kahraman M, Jeon HB, Li H, Lee JK, Suh BC, Hatcher MA, Labonte T, et al. 2004. Potent, low-calcemic, selective inhibitors of CYP24 hydroxylase: 24-Sulfone analogs of the hormone 1α,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 89-90:5–12.
  • Posner GH, Helvig C, Cuerrier D, Collop D, Kharebov A, Ryder K, Epps T, Petkovich M. 2010. Vitamin D analogues targeting CYP24 in chronic kidney disease. J Steroid Biochem Mol Biol. 121:13–19.
  • Prosser DE, Jones G. 2004. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci. 29:664–673.
  • Prosser DE, Kaufmann M, O'Leary B, Byford V, Jones G. 2007. Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into -23-hydroxylase, generating 1α,25-(OH)2D3-26,23-lactone. Proc Natl Acad Sci USA. 104:12673–12678.
  • Purnapatre K, Khattar SK, Saini KS. 2008. Cytochrome P450s in the development of target-based anticancer drugs. Cancer Lett. 259:1–15.
  • Reddy GS, Tserng KY. 1989. Calcitroic acid, end product of renal metabolism of 1,25-dihydroxyvitamin D3 through C-24 oxidation pathway. Biochemistry. 28:1763–1769.
  • Saito N, Suhara Y, Abe D, Kusudo T, Ohta M, Yasuda K, Sakaki T, Honzawa S, Fujishima T, Kittaka A. 2009. Synthesis of 2α-propoxy-1α,25-dihydroxyvitamin D3 and comparison of its metabolism by human CYP24A1 and rat CYP24A1. Bioorg Med Chem. 17:4296–4301.
  • Sakaki T, Kagawa N, Yamamoto K, Inouye K. 2005. Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 10:119–134.
  • Sakaki T, Sawada N, Komai K, Shiozawa S, Yamada S, Yamamoto K, Ohyama Y, Inouye K. 2000. Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24. Eur J Biochem. 267:6158–6165.
  • Sakaki T, Sawada N, Nonaka Y, Ohyama Y, Inouye K. 1999. Metabolic studies using recombinant Escherichia coli cells producing rat mitochondrial CYP24. CYP24 can convert 1a,25-dihydroxyvitamin D3 to calcitroic acid. Eur J Biochem. 262:43–48.
  • Schuster I, Bernhardt R. 2007. Inhibition of cytochromes P450: existing and new promising therapeutic targets. Drug Metab Rev. 39:481–499.
  • Schuster I, Egger H, Astecker N, Herzig G, Schussler M, Vorisek G. 2001. Selective inhibitors of CYP24: Mechanistic tools to explore vitamin D metabolism in human keratinocytes. Steroids. 66:451–462.
  • Schuster I, Egger H, Bikle D, Herzig G, Reddy GS, Stuetz A, Stuetz P, Vorisek G. 2001. Selective inhibition of vitamin D hydroxylases in human keratinocytes. Steroids. 66:409–422.
  • Schuster I, Egger H, Herzig G, Reddy GS, Schmid JA, Schussler M, Vorisek G. 2006. Selective inhibitors of vitamin D metabolism – new concepts and perspectives. Anticancer Res. 26:2653–2668.
  • Schuster I, Egger H, Nussbaumer P, Kroemer RT. 2003. Inhibitors of vitamin D hydroxylases: Structure-activity relationships. J Cell Biochem. 88:372–380.
  • Schuster I, Egger H, Reddy GS, Vorisek G. 2003. Combination of vitamin D metabolites with selective inhibitors of vitamin D metabolism. Recent Results Cancer Res. 164:169–188.
  • Segersten U, Holm PK, Bjorklund P, Hessman O, Nordgren H, Binderup L, Akerstrom G, Hellman P, Westin G. 2005. 25-Hydroxyvitamin D3 1α-hydroxylase expression in breast cancer and use of non-1α-hydroxylated vitamin D analogue. Breast Cancer Res. 7:R980–986.
  • Solomon JD, Heitzer MD, Liu TT, Beumer JH, Parise RA, Normolle DP, Leach DA, Buchanan G, DeFranco DB. 2014. VDR activity is differentially affected by Hic-5 in prostate cancer and stromal cells. Mol Cancer Res. 12:1166–1180.
  • Sumantran VN, Mishra P, Bera R, Sudhakar N. 2016. Microarray analysis of differentially-expressed genes encoding CYP450 and phase II drug metabolizing enzymes in psoriasis and melanoma. Pharmaceutics. 8. DOI:10.3390/pharmaceutics8010004
  • Swami S, Krishnan AV, Peehl DM, Feldman D. 2005. Genistein potentiates the growth inhibitory effects of 1,25-dihydroxyvitamin D3 in DU145 human prostate cancer cells: Role of the direct inhibition of CYP24 enzyme activity. Mol Cell Endocrinol. 241:49–61.
  • Taban IM, Zhu J, DeLuca HF, Simons C. 2017a. Analysis of the binding sites of vitamin D 1α-hydroxylase (CYP27B1) and vitamin D 24-hydroxylase (CYP24A1) for the design of selective CYP24A1 inhibitors: Homology modelling, molecular dynamics simulations and identification of key binding requirements. Bioorg Med Chem. 25:5629–5636.
  • Taban IM, Zhu J, DeLuca HF, Simons C. 2017b. Synthesis, molecular modelling and CYP24A1 inhibitory activity of novel of (E)-N-(2-(1H-imidazol-1-yl)-2-(phenylethyl)-3/4-styrylbenzamides. Bioorg Med Chem. 25:4076–4087.
  • Tashiro K, Abe T, Oue N, Yasui W, Ryoji M. 2004. Characterization of vitamin D-mediated induction of the CYP 24 transcription. Mol Cell Endocrinol. 226:27–32.
  • Tieu EW, Li W, Chen J, Kim T-K, Ma D, Slominski AT, Tuckey RC. 2015. Metabolism of 20-hydroxyvitamin D3 and 20,23-dihydroxyvitamin D3 by rat and human CYP24A1. J Steroid Biochem Mol Biol. 149:153–165.
  • Tuckey RC, Janjetovic Z, Li W, Nguyen MN, Zmijewski MA, Zjawiony J, Slominski A. 2008. Metabolism of 1α-hydroxyvitamin D3 by cytochrome P450scc to biologically active 1α,20-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 112:213–219.
  • Vantieghem K, Kissmeyer AM, De Haes P, Bouillon R, Segaert S. 2006. UVB-induced production of 1,25-dihydroxyvitamin D3 and vitamin D activity in human keratinocytes pretreated with a sterol Δ7-reductase inhibitor. J Cell Biochem. 98:81–92.
  • Vrzal R, Doricakova A, Novotna A, Bachleda P, Bitman M, Pavek P, Dvorak Z. 2011. Valproic acid augments vitamin D receptor-mediated induction of CYP24 by vitamin D3: A possible cause of valproic acid-induced osteomalacia? Toxicol Lett. 200:146–153.
  • Wegler C, Wikvall K, Norlin M. 2016. Effects of osteoporosis-inducing drugs on vitamin D-related gene transcription and mineralization in MG-63 and Saos-2 cells. Basic Clin Pharmacol Toxicol. 119:436–442.
  • Wietrzyk J. 2007. The influence of isoflavonoids on the antitumor activity of vitamin D3. Postepy Hig Med Dosw. 61:253–260. Polish.
  • Yee SW, Simons C. 2004. Synthesis and CYP24 inhibitory activity of 2-substituted-3,4-dihydro-2H-naphthalen-1-one (tetralone) derivatives. Bioorg Med Chem Lett. 14:5651–5654.
  • Zhou YK, Liang Z, Guo Y, Zhang HT, Wang KH. 2015. High glucose upregulates CYP24A1 expression which attenuates the ability of 1,25(OH)2D3 to increase NGF secretion in a rat Schwann cell line RSC96. Mol Cell Endocrinol. 404:75–81.
  • Zou A, Elgort MG, Allegretto EA. 1997. Retinoid X receptor (RXR) ligands activate the human 25-hydroxyvitamin D3-24-hydroxylase promoter via RXR heterodimer binding to two vitamin D-responsive elements and elicit additive effects with 1,25-dihydroxyvitamin D3. J Biol Chem. 272:19027–19034.

References

  • Alesutan I, Feger M, Pakladok T, Mia S, Ahmed MS, Voelkl J, Lang F. 2013. 25-Hydroxyvitamin D3 1-α-hydroxylase-dependent stimulation of renal klotho expression by spironolactone. Kidney Blood Press Res. 37:475–487.
  • Avila E, Diaz L, Barrera D, Halhali A, Mendez I, Gonzalez L, Zuegel U, Steinmeyer A, Larrea F. 2007. Regulation of vitamin D hydroxylases gene expression by 1,25-dihydroxyvitamin D3 and cyclic AMP in cultured human syncytiotrophoblasts. J Steroid Biochem Mol Biol. 103:90–96.
  • Avila E, Diaz L, Halhali A, Larrea F. 2004. Regulation of 25-hydroxyvitamin D3 1α-hydroxylase, 1,25-dihydroxyvitamin D3 24-hydroxylase and vitamin D receptor gene expression by 8-bromo cyclic AMP in cultured human syncytiotrophoblast cells. J Steroid Biochem Mol Biol. 89–90:115–119.
  • Bland R, Walker EA, Hughes SV, Stewart PM, Hewison M. 1999. Constitutive expression of 25-hydroxyvitamin D3-1α-hydroxylase in a transformed human proximal tubule cell line: evidence for direct regulation of vitamin D metabolism by calcium. Endocrinology. 140:2027–2034.
  • Bruno RD, Njar VC. 2007. Targeting cytochrome P450 enzymes: a new approach in anti-cancer drug development. Bioorg Med Chem. 15:5047–5060.
  • Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarasheski KE, Dusso AS. 2003. HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS. 17:513–520.
  • Du J, Wei X, Ge X, Chen Y, Li YC. 2017. Microbiota-dependent induction of colonic Cyp27b1 is associated with colonic inflammation: implications of locally produced 1,25-dihydroxyvitamin D3 in inflammatory regulation in the colon. Endocrinology. 158:4064–4075.
  • Ellfolk M, Norlin M, Gyllensten K, Wikvall K. 2009. Regulation of human vitamin D3 25-hydroxylases in dermal fibroblasts and prostate cancer LNCaP cells. Mol Pharmacol. 75:1392–1399.
  • Farhan H, Cross HS. 2002. Transcriptional inhibition of CYP24 by genistein. Ann NY Acad Sci. 973:459–462.
  • Farhan H, Wähälä K, Cross HS. 2003. Genistein inhibits vitamin D hydroxylases CYP24 and CYP27B1 expression in prostate cells. J Steroid Biochem Mol Biol. 84:423–429.
  • Frizen BN, Zhegin VA. 1976. Clinico-functional characteristics of the esophagus in rheumatoid arthritis and systemic lupus erythematosus in comparison with systemic scleroderma. Terapevticheskii Arkhiv. 48:57–64. Russian.
  • Ge N, Chu XM, Xuan YP, Ren DQ, Wang Y, Ma K, Gao HJ, Jiao WJ. 2017. Associations between abnormal vitamin D metabolism pathway function and non-small cell lung cancer. Oncol Lett. 14:7538–7544.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Inouye K, Sakaki T. 2001. Enzymatic studies on the key enzymes of vitamin D metabolism; 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24). Biotechnol Annu Rev. 7:179–194.
  • Kim CJ, Kaplan LE, Perwad F, Huang N, Sharma A, Choi Y, Miller WL, Portale AA. 2007. Vitamin D 1α-hydroxylase gene mutations in patients with 1α-hydroxylase deficiency. J Clin Endocrinol Metab. 92:3177–3182.
  • Kitanaka S, Takeyama K, Murayama A, Sato T, Okumura K, Nogami M, Hasegawa Y, Niimi H, Yanagisawa J, Tanaka T, et al. 1998. Inactivating mutations in the 25-hydroxyvitamin D3 1α-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. New Engl J Med. 338:653–661.
  • Kozai M, Yamamoto H, Ishiguro M, Harada N, Masuda M, Kagawa T, Takei Y, Otani A, Nakahashi O, Ikeda S, et al. 2013. Thyroid hormones decrease plasma 1α,25-dihydroxyvitamin D levels through transcriptional repression of the renal 25-hydroxyvitamin D3 1α-hydroxylase gene (CYP27B1). Endocrinology. 154:609–622.
  • Lechner D, Bajna E, Adlercreutz H, Cross HS. 2006. Genistein and 17β-estradiol, but not equol, regulate vitamin D synthesis in human colon and breast cancer cells. Anticancer Res. 26:2597–2603.
  • Lechner D, Kallay E, Cross HS. 2007. 1α,25-Dihydroxyvitamin D3 downregulates CYP27B1 and induces CYP24A1 in colon cells. Mol Cell Endocrinol. 263:55–64.
  • Maas RM, Reus K, Diesel B, Steudel WI, Feiden W, Fischer U, Meese E. 2001. Amplification and expression of splice variants of the gene encoding the P450 cytochrome 25-hydroxyvitamin D3 1,α-hydroxylase (CYP 27B1) in human malignant glioma. Clin Cancer Res. 7:868–875.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Pascussi JM, Robert A, Nguyen M, Walrant-Debray O, Garabedian M, Martin P, Pineau T, Saric J, Navarro F, Maurel P, et al. 2005. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 115:177–186.
  • Portale AA, Miller WL. 2000. Human 25-hydroxyvitamin D-1a-hydroxylase: cloning, mutations, and gene expression. Pediatr Nephrol. 14:620–625.
  • Sakaki T, Kagawa N, Yamamoto K, Inouye K. 2005. Metabolism of vitamin D3 by cytochromes P450. Front Biosci. 10:119–134.
  • Schuster I, Egger H, Bikle D, Herzig G, Reddy GS, Stuetz A, Stuetz P, Vorisek G. 2001. Selective inhibition of vitamin D hydroxylases in human keratinocytes. Steroids. 66:409–422.
  • Schuster I, Egger H, Herzig G, Reddy GS, Schmid JA, Schussler M, Vorisek G. 2006. Selective inhibitors of vitamin D metabolism–new concepts and perspectives. Anticancer Res. 26:2653–2668.
  • Schuster I, Egger H, Nussbaumer P, Kroemer RT. 2003. Inhibitors of vitamin D hydroxylases: Structure-activity relationships. J Cell Biochem. 88:372–380.
  • Schuster I, Egger H, Reddy GS, Vorisek G. 2003. Combination of vitamin D metabolites with selective inhibitors of vitamin D metabolism. Recent Results Cancer Res. 164:169–188.
  • Smith SJ, Rucka AK, Berry JL, Davies M, Mylchreest S, Paterson CR, Heath DA, Tassabehji M, Read AP, Mee AP, et al. 1999. Novel mutations in the 1α-hydroxylase (P450c1) gene in three families with pseudovitamin D-deficiency rickets resulting in loss of functional enzyme activity in blood-derived macrophages. J Bone Mineral Res. 14:730–739.
  • Somjen D, Katzburg S, Stern N, Kohen F, Sharon O, Limor R, Jaccard N, Hendel D, Weisman Y. 2007. 25-Hydroxy vitamin D3-1α hydroxylase expression and activity in cultured human osteoblasts and their modulation by parathyroid hormone, estrogenic compounds and dihydrotestosterone. J Steroid Biochem Mol Biol. 107:238–244.
  • Somjen D, Knoll E, Sharon O, Many A, Stern N. 2017. Interaction between the effects of the selective estrogen modulator femarelle and a vitamin D analog in human umbilical artery vascular smooth muscle cells. J Steroid Biochem Mol Biol. 174:9–13.
  • Somjen D, Weisman Y, Kohen F, Gayer B, Limor R, Sharon O, Jaccard N, Knoll E, Stern N. 2005. 25-Hydroxyvitamin D3-1α-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation. 111:1666–1671.
  • Sumantran VN, Mishra P, Bera R, Sudhakar N. 2016. Microarray analysis of differentially-expressed genes encoding CYP450 and Phase II drug metabolizing enzymes in psoriasis and melanoma. Pharmaceutics 8. DOI:10.3390/pharmaceutics8010004
  • Tang EKY, Chen JJ, Janjetovic Z, Tieu EW, Slominski AT, Li W, Tuckey RC. 2013. Hydroxylation of CYP11A1-derived products of vitamin D3 metabolism by human and mouse CYP27B1. Drug Metab Dispos. 41:1112–1124.
  • Wang JT, Lin CJ, Burridge SM, Fu GK, Labuda M, Portale AA, Miller WL. 1998. Genetics of vitamin D 1α-hydroxylase deficiency in 17 families. Am J Hum Genet. 63:1694–1702.
  • Wegler C, Wikvall K, Norlin M. 2016. Effects of osteoporosis-inducing drugs on vitamin D-related gene transcription and mineralization in MG-63 and Saos-2 cells. Basic Clin Pharmacol Toxicol. 119:436–442.
  • Wietrzyk J. 2007. The influence of isoflavonoids on the antitumor activity of vitamin D3. Postepy Hig Med Dosw. 61:253–260. Polish.
  • Wu S, Ren S, Nguyen L, Adams JS, Hewison M. 2007. Splice variants of the CYP27b1 gene and the regulation of 1,25-dihydroxyvitamin D3 production. Endocrinology. 148:3410–3418.
  • Xie Z, Munson SJ, Huang N, Portale AA, Miller WL, Bikle DD. 2002. The mechanism of 1,25-dihydroxyvitamin D3 autoregulation in keratinocytes. J Biol Chem. 277:36987–36990.
  • Zhalehjoo N, Shakiba Y, Panjehpour M. 2017. Gene expression profiles of CYP24A1 and CYP27B1 in malignant and normal breast tissues. Mol Med Rep. 15:467–473.

References

  • Armstrong JL, Ruiz M, Boddy AV, Redfern CP, Pearson AD, Veal GJ. 2005. Increasing the intracellular availability of all-trans retinoic acid in neuroblastoma cells. Brit J Cancer. 92:696–704.
  • Brown GT, Cash BG, Blihoghe D, Johansson P, Alnabulsi A, Murray GI. 2014. The expression and prognostic significance of retinoic acid metabolising enzymes in colorectal cancer. PloS One. 9:e90776.
  • Chang CL, Hong E, Lao-Sirieix P, Fitzgerald RC. 2008. A novel role for the retinoic acid-catabolizing enzyme CYP26A1 in Barrett's associated adenocarcinoma. Oncogene. 27:2951–2960.
  • Diaz P, Huang W, Keyari CM, Buttrick B, Price L, Guilloteau N, Tripathy S, Sperandio VG, Fronczek FR, Astruc-Diaz F, et al. 2016. Development and characterization of novel and selective inhibitors of cytochrome P450 CYP26A1, the human liver retinoic acid hydroxylase. J Med Chem. 59:2579–2595.
  • Gomaa MS, Bridgens CE, Aboraia AS, Veal GJ, Redfern CP, Brancale A, Armstrong JL, Simons C. 2011. Small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26): synthesis and biological evaluation of imidazole methyl 3-(4-(aryl-2-ylamino)phenyl)propanoates. J Med Chem. 54:2778–2791.
  • Gomaa MS, Bridgens CE, Veal GJ, Redfern CP, Brancale A, Armstrong JL, Simons C. 2011. Synthesis and biological evaluation of 3-(1H-imidazol- and triazol-1-yl)-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propyl derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26). J Med Chem. 54:6803–6811.
  • Gudas LJ. 2012. Emerging roles for retinoids in regeneration and differentiation in normal and disease states. Biochim Biophys Acta. 1821:213–221.
  • Helvig C, Taimi M, Cameron D, Jones G, Petkovich M. 2011. Functional properties and substrate characterization of human CYP26A1, CYP26B1, and CYP26C1 expressed by recombinant baculovirus in insect cells. J Pharmacol Toxicol Methods. 64:258–263.
  • Hogarth CA, Griswold MD. 2013. Retinoic acid regulation of male meiosis. Curr Opin Endocrinol Diabetes Obes. 20:217–223.
  • Lampen A, Meyer S, Arnhold T, Nau H. 2000. Metabolism of vitamin A and its active metabolite all-trans-retinoic acid in small intestinal enterocytes. J Pharmacol Exp Ther. 295:979–985.
  • Lutz JD, Dixit V, Yeung CK, Dickmann LJ, Zelter A, Thatcher JE, Nelson WL, Isoherranen N. 2009. Expression and functional characterization of cytochrome P450 26A1, a retinoic acid hydroxylase. Biochem Pharmacol. 77:258–268.
  • Maden M. 2007. Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci. 8:755–765.
  • Napoli JL. 2012. Physiological insights into all-trans-retinoic acid biosynthesis. Biochim Biophys Acta. 1821:152–167.
  • Nelson CH, Buttrick BR, Isoherranen N. 2013. Therapeutic potential of the inhibition of the retinoic acid hydroxylases CYP26A1 and CYP26B1 by xenobiotics. Curr Topics Med Chem. 13:1402–1428.
  • Njar VC. 2002. Cytochrome P450 retinoic acid 4-hydroxylase inhibitors: potential agents for cancer therapy. MiniRev Med Chem. 2:261–269.
  • Njar VC, Gediya L, Purushottamachar P, Chopra P, Vasaitis TS, Khandelwal A, Mehta J, Huynh C, Belosay A, Patel J. 2006. Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases. Bioorg Med Chem. 14:4323–4340.
  • Ocaya P, Gidlöf AC, Olofsson PS, Törmä H, Sirsjö A. 2007. CYP26 inhibitor R115866 increases retinoid signaling in intimal smooth muscle cells. Arterioscler Thromb Vasc Biol. 27:1542–1548.
  • Osanai M, Lee GH. 2011a. Enhanced expression of retinoic acid-metabolizing enzyme CYP26A1 in sunlight-damaged human skin. Med Mol Morphol. 44:200–206.
  • Osanai M, Lee GH. 2011b. Nicotine-mediated suppression of the retinoic acid metabolizing enzyme CYP26A1 limits the oncogenic potential of breast cancer. Cancer Sci. 102:1158–1163.
  • Osanai M, Lee GH. 2014. Increased expression of the retinoic acid-metabolizing enzyme CYP26A1 during the progression of cervical squamous neoplasia and head and neck cancer. BMC Res Notes. 7:697.
  • Osanai M, Lee GH. 2015. The retinoic acid-metabolizing enzyme CYP26A1 upregulates fascin and promotes the malignant behavior of breast carcinoma cells. Oncol Rep. 34:850–858.
  • Ozpolat B, Mehta K, Lopez-Berestein G. 2005. Regulation of a highly specific retinoic acid-4-hydroxylase (CYP26A1) enzyme and all-trans-retinoic acid metabolism in human intestinal, liver, endothelial, and acute promyelocytic leukemia cells. Leuk Lymphoma. 46:1497–1506.
  • Ozpolat B, Mehta K, Tari AM, Lopez-Berestein G. 2002. All-trans-Retinoic acid-induced expression and regulation of retinoic acid 4-hydroxylase (CYP26) in human promyelocytic leukemia. Am J Hematol. 70:39–47.
  • Ozpolat B, Tari AM, Mehta K, Lopez-Berestein G. 2004. Nuclear retinoid receptors are involved in N-(4-hydroxyphenyl) retinamide (Fenretinide)-induced gene expression and growth inhibition in HL-60 acute myeloid leukemia cells. Leuk Lymphoma. 45:979–985.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Pavez Lorie E, Chamcheu JC, Vahlquist A, Torma H. 2009. Both all-trans retinoic acid and cytochrome P450 (CYP26) inhibitors affect the expression of vitamin A metabolizing enzymes and retinoid biomarkers in organotypic epidermis. Arch Dermatol Res. 301:475–485.
  • Pavez Lorie E, Cools M, Borgers M, Wouters L, Shroot B, Hagforsen E, Torma H, Vahlquist A. 2009. Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of retinoid-regulated genes in normal human epidermis. Brit J Dermatol. 160:26–36.
  • Pavez Lorie E, Li H, Vahlquist A, Torma H. 2009. The involvement of cytochrome P450 (CYP) 26 in the retinoic acid metabolism of human epidermal keratinocytes. Biochim Biophys Acta. 1791:220–228.
  • Purushottamachar P, Patel JB, Gediya LK, Clement OO, Njar VC. 2012. First chemical feature-based pharmacophore modeling of potent retinoidal retinoic acid metabolism blocking agents (RAMBAs): identification of novel RAMBA scaffolds. Eur J Med Chem. 47:412–423.
  • Quere R, Baudet A, Cassinat B, Bertrand G, Marti J, Manchon L, Piquemal D, Chomienne C, Commes T. 2007. Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 109:4450–4460.
  • Ricard MJ, Gudas LJ. 2013. Cytochrome P450 cyp26a1 alters spinal motor neuron subtype identity in differentiating embryonic stem cells. J Biol Chem. 288:28801–28813.
  • Ross AC. 2012. Vitamin A and retinoic acid in T cell-related immunity. Am J Clin Nutr. 96:1166s–1172s.
  • Ross AC, Zolfaghari R. 2011. Cytochrome P450s in the regulation of cellular retinoic acid metabolism. Annu Rev Nutr. 31:65–87.
  • Schuster I, Bernhardt R. 2007. Inhibition of cytochromes P450: existing and new promising therapeutic targets. Drug Metab Rev. 39:481–499.
  • Shimshoni JA, Roberts AG, Scian M, Topletz AR, Blankert SA, Halpert JR, Nelson WL, Isoherranen N. 2012. Stereoselective formation and metabolism of 4-hydroxy-retinoic acid enantiomers by cytochrome P450 enzymes. J Biol Chem. 287:42223–42232.
  • Sun B, Liu K, Han J, Zhao LY, Su X, Lin B, Zhao DM, Cheng MS. 2015. Design, synthesis, and biological evaluation of amide imidazole derivatives as novel metabolic enzyme CYP26A1 inhibitors. Bioorg Med Chem. 23:6763–6773.
  • Sun B, Song S, Hao CZ, Huang WX, Liu CC, Xie HL, Lin B, Cheng MS, Zhao DM. 2015. Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents. J Mol Graph Model. 56:10–19.
  • Tay S, Dickmann L, Dixit V, Isoherranen N. 2010. A comparison of the roles of peroxisome proliferator-activated receptor and retinoic acid receptor on CYP26 regulation. Mol Pharmacol. 77:218–227.
  • Thatcher JE, Buttrick B, Shaffer SA, Shimshoni JA, Goodlett DR, Nelson WL, Isoherranen N. 2011. Substrate specificity and ligand interactions of CYP26A1, the human liver retinoic acid hydroxylase. Mol Pharmacol. 80:228–239.
  • Thatcher JE, Isoherranen N. 2009. The role of CYP26 enzymes in retinoic acid clearance. Expert Opin Drug Metab Toxicol. 5:875–886.
  • Thatcher JE, Zelter A, Isoherranen N. 2010. The relative importance of CYP26A1 in hepatic clearance of all-trans retinoic acid. Biochem Pharmacol. 80:903–912.
  • Topletz AR, Thatcher JE, Zelter A, Lutz JD, Tay S, Nelson WL, Isoherranen N. 2012. Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases. Biochem Pharmacol. 83:149–163.
  • Topletz AR, Tripathy S, Foti RS, Shimshoni JA, Nelson WL, Isoherranen N. 2015. Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids. Mol Pharmacol. 87:430–441.
  • Villani MG, Appierto V, Cavadini E, Valsecchi M, Sonnino S, Curley RW, Formelli F. 2004. Identification of the fenretinide metabolite 4-oxo-fenretinide present in human plasma and formed in human ovarian carcinoma cells through induction of cytochrome P450 26A1. Clin Cancer Res. 10:6265–6275.
  • Wang F, Kwak HS, Elbuluk N, Kaczmarek AL, Hamilton T, Voorhees JJ, Fisher GJ, Kang S. 2009. Retinoic acid 4-hydroxylase inducibility and clinical response to isotretinoin in patients with acne. J Am Acad Dermatol. 61:252–258.
  • Yee SW, Jarno L, Gomaa MS, Elford C, Ooi LL, Coogan MP, McClelland R, Nicholson RI, Evans BA, Brancale A, et al. 2005. Novel tetralone-derived retinoic acid metabolism blocking agents: synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays. J Med Chem. 48:7123–7131.

References

  • Bechor S, Zolberg Relevy N, Harari A, Almog T, Kamari Y, Ben-Amotz A, Harats D, Shaish A. 2016. 9-cis β-Carotene increased cholesterol efflux to HDL in macrophages. Nutrients. 8:435.
  • Brown GT, Cash BG, Blihoghe D, Johansson P, Alnabulsi A, Murray GI. 2014. The expression and prognostic significance of retinoic acid metabolising enzymes in colorectal cancer. PloS One. 9:e90776.
  • Diaz P, Huang W, Keyari CM, Buttrick B, Price L, Guilloteau N, Tripathy S, Sperandio VG, Fronczek FR, Astruc-Diaz F, et al. 2016. Development and characterization of novel and selective inhibitors of cytochrome P450 CYP26A1, the human liver retinoic acid hydroxylase. J Med Chem. 59:2579–2595.
  • Downie D, McFadyen MC, Rooney PH, Cruickshank ME, Parkin DE, Miller ID, Telfer C, Melvin WT, Murray GI. 2005. Profiling cytochrome P450 expression in ovarian cancer: identification of prognostic markers. Clin Cancer Res. 11:7369–7375.
  • Guengerich FP. 2015. Chapter 9, Human cytochrome P450 enzymes. In: Ortiz de Montellano PR, editor. Cytochrome P450: structure, mechanism, and biochemistry. 4th ed. New York (NY): Springer; p. 523–785.
  • Helvig C, Taimi M, Cameron D, Jones G, Petkovich M. 2011. Functional properties and substrate characterization of human CYP26A1, CYP26B1, and CYP26C1 expressed by recombinant baculovirus in insect cells. J Pharmacol Toxicol Methods. 64:258–263.
  • Kumar S, Chatzi C, Brade T, Cunningham TJ, Zhao X, Duester G. 2011. Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling. Nat Commun. 2:151.
  • Njar VC. 2002. Cytochrome P450 retinoic acid 4-hydroxylase inhibitors: potential agents for cancer therapy. Mini Rev Med Chem. 2:261–269.
  • Njar VC, Gediya L, Purushottamachar P, Chopra P, Vasaitis TS, Khandelwal A, Mehta J, Huynh C, Belosay A, Patel J. 2006. Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases. Bioorg Med Chem. 14:4323–4340.
  • Ocaya P, Gidlöf AC, Olofsson PS, Törmä H, Sirsjö A. 2007. CYP26 inhibitor R115866 increases retinoid signaling in intimal smooth muscle cells. Arterioscler Thromb Vasc Biol. 27:1542–1548.
  • Ocaya PA, Elmabsout AA, Olofsson PS, Torma H, Gidlof AC, Sirsjo A. 2011. CYP26B1 plays a major role in the regulation of all-trans-retinoic acid metabolism and signaling in human aortic smooth muscle cells. J Vasc Res. 48:23–30.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Pavez Lorie E, Chamcheu JC, Vahlquist A, Torma H. 2009. Both all-trans retinoic acid and cytochrome P450 (CYP26) inhibitors affect the expression of vitamin A metabolizing enzymes and retinoid biomarkers in organotypic epidermis. Arch Dermatol Res. 301:475–485.
  • Pavez Lorie E, Cools M, Borgers M, Wouters L, Shroot B, Hagforsen E, Torma H, Vahlquist A. 2009. Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of retinoid-regulated genes in normal human epidermis. Brit J Dermatol. 160:26–36.
  • Pavez Lorie E, Li H, Vahlquist A, Torma H. 2009. The involvement of cytochrome P450 (CYP) 26 in the retinoic acid metabolism of human epidermal keratinocytes. Biochim Biophys Acta. 1791:220–228.
  • Ross AC, Zolfaghari R. 2011. Cytochrome P450s in the regulation of cellular retinoic acid metabolism. Annu Rev Nutr. 31:65–87.
  • Taimi M, Helvig C, Wisniewski J, Ramshaw H, White J, Amad M, Korczak B, Petkovich M. 2004. A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid. J Biol Chem. 279:77–85.
  • Topletz AR, Thatcher JE, Zelter A, Lutz JD, Tay S, Nelson WL, Isoherranen N. 2012. Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases. Biochem Pharmacol. 83:149–163.

References

  • Helvig C, Taimi M, Cameron D, Jones G, Petkovich M. 2011. Functional properties and substrate characterization of human CYP26A1, CYP26B1, and CYP26C1 expressed by recombinant baculovirus in insect cells. J Pharmacol Toxicol Methods. 64:258–263.
  • Osanai M, Lee GH. 2016. Elevated expression of the retinoic acid-metabolizing enzyme CYP26C1 in primary breast carcinomas. Med Mol Morphol. 49:22–27.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17. DOI:10.3390/ijms17071020
  • Ross AC, Zolfaghari R. 2011. Cytochrome P450s in the regulation of cellular retinoic acid metabolism. Annu Rev Nutr. 31:65–87.
  • Taimi M, Helvig C, Wisniewski J, Ramshaw H, White J, Amad M, Korczak B, Petkovich M. 2004. A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid. J Biol Chem. 279:77–85.
  • Xi J, Yang Z. 2008. Expression of RALDHs (ALDH1As) and CYP26s in human tissues and druing the neural differentiation of P19 embryonal carcinoma stem cell. Gene Expr Patterns 8:438–442.
  • Zhong G, Ortiz D, Zelter A, Nath A, Isoherranen N. (2018) CYP26C1 is a hydroxylase of multiple active retinoids and interacts with cellular retinoic acid binding proteins. Mol Pharmacol. 93:489–503.

References

  • Andersson E, Bjorklind C, Torma H, Vahlquist A. 1994. The metabolism of vitamin A to 3,4-didehydroretinol can be demonstrated in human keratinocytes, melanoma cells and HeLa cells, and is correlated to cellular retinoid-binding protein expression. Biochim Biophys Acta. 1224:349–354.
  • Enright JM, Toomey MB, Sato SY, Temple SE, Allen JR, Fujiwara R, Kramlinger VM, Nagy LD, Johnson KM, Xiao Y, et al. 2015. Cyp27c1 red-shifts the spectral sensitivity of photoreceptors by converting vitamin A1 into A2. Curr Biol. 25:3048–3057.
  • Johnson KM, Phan TTN, Albertolle ME, Guengerich FP. 2017. Human mitochondrial cytochrome P450 27C1 is localized in skin and preferentially desaturates trans-retinol to 3,4-dehydroretinol. J Biol Chem. 292:13672–13687.
  • Kramlinger VM, Nagy LD, Fujiwara R, Johnson KM, Phan TT, Xiao Y, Enright JM, Toomey MB, Corbo JC, Guengerich FP. 2016. Human cytochrome P450 27C1 catalyzes 3,4-desaturation of retinoids. FEBS Lett. 590:1304–1312.
  • Pan ST, Xue D, Li ZL, Zhou ZW, He ZX, Yang Y, Yang T, Qiu JX, Zhou SF. 2016. Computational identification of the paralogs and orthologs of human cytochrome P450 superfamily and the implication in drug discovery. Int J Mol Sci. 17(7). pii: ijms17071020.
  • Rollman O, Wood EJ, Olsson MJ, Cunliffe WJ. 1993. Biosynthesis of 3,4-didehydroretinol from retinol by human skin keratinocytes in culture. Biochem J. 293:675–682.
  • Tafrova JI, Pinkas-Sarafova A, Stolarzewicz E, Parker KA, Simon M. 2012. UVA/B exposure promotes the biosynthesis of dehydroretinol in cultured human keratinocytes. Mol Cell Biochem. 364:351–361.
  • Törmä H, Stenström E, Andersson E, Vahlquist A. 1991. Synthetic retinoids affect differently the epidermal synthesis of 3,4-didehydroretinol. Skin Pharmacol. 4:246–253.
  • Törmä H, Vahlquist A. 1985. Biosynthesis of 3-dehydroretinol (vitamin A2) from all-trans-retinol (vitamin A1) in human epidermis. J Invest Dermatol. 85:498–500.
  • Vahlquist A. 1980. The identification of dehydroretinol (vitamin A2) in human skin. Experientia. 36:317–318.
  • Vahlquist A. 1982. Vitamin A in human skin: I. Detection and identification of retinoids in normal epidermis. J Invest Dermatol. 79:89–93.
  • Vahlquist A, Andersson E, Coble BI, Rollman O, Törmä H. 1996. Increased concentrations of 3,4-didehydroretinol and retinoic acid-binding protein (CRABPII) in human squamous cell carcinoma and keratoacanthoma but not in basal cell carcinoma of the skin. J Invest Dermatol. 106:1070–1074.
  • Vahlquist A, Lee JB, Michaelsson G, Rollman O. 1982. Vitamin A in human skin: II. Concentrations of carotene, retinol and dehydroretinol in various components of normal skin. J Invest Dermatol. 79:94–97.

References

  • Guengerich FP, Cheng Q. 2011. Orphans in the human cytochrome P450 superfamily: approaches to discovering functions and relevance in pharmacology. Pharmacol Rev. 63:684–699.
  • Lemaire B, Kubota A, O'Meara CM, Lamb DC, Tanguay RL, Goldstone JV, Stegeman JJ. 2016. Cytochrome P450 20A1 in zebrafish: cloning, regulation and potential involvement in hyperactivity disorders. Toxicol Appl Pharmacol. 296:73–84.
  • Marek CJ, Tucker SJ, Koruth M, Wallace K, Wright MC. 2007. Expression of CYP2S1 in human hepatic stellate cells. FEBS Lett. 581:781–786.
  • Stark K, Guengerich FP. 2007. Characterization of orphan human cytochromes P450. Drug Metab Rev. 39:627–637.
  • Stark K, Wu ZL, Bartleson CJ, Guengerich FP. 2008. mRNA distribution and heterologous expression of orphan cytochrome P450 20A1. Drug Metab Dispos. 36:1930–1937.

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