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Review Article

Regioselective hydroxylation of steroid hormones by human cytochromes P450

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Pages 89-110 | Received 27 Dec 2014, Accepted 21 Jan 2015, Published online: 13 Feb 2015

References

  • Agrawa V, Choi JH, Giacomini KM, Miller WL. (2010). Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase. Pharmacogenet Genomics 20:611–618
  • 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
  • Badawi AF, Cavalieri EL, Rogan EG. (2001). Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16α-hydroxylation of 17β-estradiol. Metabolism 50:1001–1003
  • Cao PR, Bernhardt R. (1999). Interaction of CYP11B1 (cytochrome P-45011β) with CYP11A1 (cytochrome P-450scc) in COS-1 cells. Eur J Biochem 262:720–726
  • Cheng Q, Sohl CD, Yoshimoto FK, Guengerich FP. (2012). Oxidation of dihydrotestosterone by human cytochromes P450 19A1 and 3A4. J Biol Chem 287:29554–29567
  • Cheng Z, Shu Y, Liu Z, et al. (2000). Role of cytochrome P450 in estradiol metabolism in vitro. Acta Pharmacol Sin 22:148–154
  • Choi MH, Skipper PL, Wishnok JS, Tannenbaum SR. (2005). Characterization of testosterone 11β-hydroxylation catalyzed by human liver microsomal cytochromes P450. Drug Metab Dispos 33:714–718
  • Choi SY, Koh KH, Jeong H. (2013). Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos 41:263–269
  • Cribb AE, Knight MJ, Dryer D, et al. (2006). Role of polymorphic human cytochrome P450 enzymes in estrone oxidation. Cancer Epidemiol Biomarkers Prev 15:551–558
  • Deo AK, Bandiera SM. (2008). Identification of human hepatic cytochrome P450 enzymes involved in the biotransformation of cholic and chenodeoxycholic acid. Drug Metab Dispos 36:1983–1991
  • Diczfalusy U, Björkhem I. (2011). Still another activity by the highly promiscuous enzyme CYP3A4: 25-hydroxylation of cholesterol. Lipid Res 52:1447–1449
  • Diczfalusy U, Kanebratt KP, Bredberg E, et al. (2009). 4β-Hydroxycholesterol as an endogenous marker for CYP3A4/5 activity. Stability and half-life of elimination after induction with rifampicin. Br J Clin Pharmacol 67:38–43
  • Diczfalusy U, Nylén H, Elander P, Bertilsson L. (2011). 4β-Hydroxycholesterol, an endogenous marker of CYP3A4/5 activity in humans. Br J Clin Pharmacol 71:183–189
  • Enberg U, Volpe C, Hamberger B. (2003). New aspects on primary aldosteronism. Neurochem Res 28:327–332
  • Flück CE, Miller WL, Auchus RJ. (2003). The 17,20-lyase activity of cytochrome p450c17 from human fetal testis favors the Δ5 steroidogenic pathway. J Clin Endocrinol Metab 88:3762–3766
  • Gillam EM, Baba T, Kim B-R, et al. (1993). Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch Biochem Biophys 305:123–131
  • Gomes LG, Huang N, Agrawal V, et al. (2009). Extraadrenal 21-hydroxylation by CYP2C19 and CYP3A4: Effect on 21-hydroxylase deficiency. J Clin Endocrinol Metab 94:89–95
  • Hiroi T, Kishimoto W, Cho T, et al. (2001). Progesterone oxidation by cytochrome P450 2D isoforms in the brain. Endocrinology 142:3901–3908
  • Honda A, Miyazaki T, Ikegami T, et al. (2011). Cholesterol 25-hydroxylation activity of CYP3A. J Lipid Res 52:1509–1516
  • Imai T, Globerman H, Gertner JM, et al. (1993). Expression and purification of functional human 17α-hydroxylase/17,20-lyase (P450c17) in Escherichia coli. Use of this system for study of a novel form of combined 17α-hydroxylase/17,20-lyase deficiency. J Biol Chem 268:19681–19689
  • Imaoka S, Yamada T, Hiroi T, et al. (1996). Multiple forms of human P450 expressed in Saccharomyces cerevisiae. Systematic characterization and comparison with those of the rat. Biochem Pharmacol 51:1041–1050
  • Isoherranen N, Thummel KE. (2013). Drug metabolism and transport during pregnancy: How does drug disposition change during pregnancy and what are the mechanisms that cause such changes? Drug Metab Dispos 41:256–262
  • Jansson I, Stoilov I, Sarfarazi M, Schenkman JB. (2001). Effect of two mutations of human CYP1B1, G61E and R469W, on stability and endogenous steroid substrate metabolism. Pharmacogenetics 11:793–801
  • Kagawa N, Hori H, Waterman MR, Yoshioka S. (2004). Characterization of stable human aromatase expressed in E. coli. Steroids 69:235–243
  • Katagiri M, Kagawa N, Waterman MR. (1995). The role of cytochrome b5 in the biosynthesis of androgens by human P450c17. Arch Biochem Biophys 317:343–347
  • Kellis JT Jr, Vickery LE. (1987). Purification and characterization of human placental aromatase cytochrome P-450. J Biol Chem 262:4413–4420
  • Kenworthy KE, Clarke SE, Andrews J, Houston JB. (2001). Multisite kinetic models for CYP3A4: Simultaneous activation and inhibition of diazepam and testosterone metabolism. Drug Metab Dispos 29:1644–1651
  • Kerlan V, Dreano Y, Bercovici JP, et al. (1992). Nature of cytochromes P450 involved in the 2-/4-hydroxylations of estradiol in human liver microsomes. Biochem Pharmacol 44:1745–1756
  • Kishimoto W, Hiroi T, Shiraishi M, et al. (2004). Cytochrome P450 2D catalyze steroid 21-hydroxylation in the brain. Endocrinology 145:699–705
  • Kohalmy K, Tamási V, Kóbori L, et al. (2007). Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor. Drug Metab Dispos 35:1495–1501
  • Lee AJ, Cai MX, Thomas PE, et al. (2003a). Characterization of the oxidative metabolites of 17β-estradiol and estrone formed by 15 selectively expressed human cytochrome P450 isoforms. Endocrinology 144:3382–3398
  • Lee AJ, Conney AH, Zhu BT. (2003b). Human cytochrome P450 3A7 has a distinct high catalytic activity for the 16α-hydroxylation of estrone but not 17β-estradiol. Cancer Res 63:6532–6536
  • Lee SJ, Goldstein JA. (2012). Comparison of CYP3A4 and CYP3A5: The effects of cytochrome b5 and NADPH-cytochrome P450 reductase on testosterone hydroxylation activities. Drug Metab Pharmacokinet 27:663–667
  • Lee-Robichaud P, Wright JN, Akhtar ME, Akhtar M. (1995). Modulation of the activity of human 17α-hydroxylase-17,20-lyase (CYP17) by cytochrome b5: Endocrinological and mechanistic implications. Biochem J 308:901–908
  • Lu F, Zahid M, Saeed M, et al. (2007). Estrogen metabolism and formation of estrogen-DNA adducts in estradiol-treated MCF-10F cells. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction and catechol-O-methyltransferase inhibition. J Steroid Biochem Mol Biol 105:150–158
  • Mäenpää J, Pelkonen O, Cresteil T, Rane A. (1993). The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol 44:61–67
  • Masimirembwa CM, Otter C, Berg M, et al. (1999). Heterologous expression and kinetic characterization of human cytochromes P-450: Validation of a pharmaceutical tool for drug metabolism research. Drug Metab Dispos 27:1117–1122
  • Miller KK, Cai J, Ripp SL, et al. (2004). Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450. Drug Metab Dispos 32:305–313
  • Miyazaki M, Nakamura K, Fujita Y, et al. (2008). Defective activity of recombinant cytochromes P450 3A4.2 and 3A4.16 in oxidation of midazolam, nifedipine, and testosterone. Drug Metab Dispos 36:2287–2291
  • Monostory K, Dvorak Z. (2011). Steroid regulation of drug-metabolizing cytochromes P450. Curr Drug Metab 12:154–172
  • Mulatero P, Curnow KM, Aupetit-Faisant B, et al. (1998). Recombinant CYP11B genes encode enzymes that can catalyze conversion of 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol. J Clin Endocrinol Metab 83:3996–4001
  • Nakamura H, Nakasa H, Ishii I, et al. (2002). Effects of endogenous steroids on CYP3A4-mediated drug metabolism by human liver microsomes. Drug Metab Dispos 30:534–540
  • Nakamura H, Torimoto N, Ishii I, et al. (2003). CYP3A4 and CYP3A7-mediated carbamazepine 10,11-epoxidation are activated by differential endogenous steroids. Drug Metab Dispos 31:432–438
  • Niwa T, Hiroi T, Tsuzuki D, et al. (2004). Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Mol Brain Res 129:117–123
  • Niwa T, Imamura H, Katagiri M. (2012). Inhibition of human steroidogenic cytochrome P450 c17 by 21-hydroxypregnenolone and related steroid hormones. Biol Pharm Bull 35:1594–1597
  • Niwa T, Kageyama A, Kishimoto K, et al. (2002). Amino acid residues affecting the activities of human cytochrome P450 2C9 and 2C19. Drug Metab Dispos 30:931–936
  • Niwa T, Murayama N, Emoto C, Yamazaki H. (2009a). Comparison of kinetic parameters for drug oxidation rates and substrate inhibition potential mediated by cytochrome P450 3A4 and 3A5. Curr Drug Metab 9:20–33
  • Niwa T, Murayama N, Yamazaki H. (2008a). Heterotropic cooperativity in oxidation mediated by cytochrome P450. Curr Drug Metab 9:453–462
  • Niwa T, Murayama N, Yamazaki H. (2009b). Oxidation of endobiotics mediated by xenobiotic-metabolizing forms of human cytochrome P450. Curr Drug Metab 10:700–712
  • Niwa T, Murayama N, Yamazaki H. (2010a). Comparison of cytochrome P450 2D6 and variants in terms of drug oxidation rates and substrate inhibition. Curr Drug Metab 12:412–435
  • Niwa T, Murayama N, Yamazaki H. (2010b). Comparison of the contributions of cytochrome P450 3A4 and 3A5 in drug oxidation rates and substrate inhibition. J Health Sci 56:239–256
  • Niwa T, Okada K, Hiroi T, et al. (2008b). Effect of psychotropic drugs on the 21-hydroxylation of neurosteroids, progesterone and allopregnanolone, catalyzed by rat CYP2D4 and human CYP2D6 in the brain. Biol Pharm Bull 31:348–351
  • Niwa T, Shiraga T, Yamasaki S, et al. (2003). In vitro activation of 7-benzyloxyresorufin O-debenzylation and nifedipine oxidation in human liver microsomes. Xenobiotica 33:717–729
  • Niwa T, Yabusaki Y, Honma K, et al. (1998). Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica 28:539–547
  • Niwa T, Yamazaki H. (2011). Comparison of cytochrome P450 2C subfamily members in terms of drug oxidation rates and substrate inhibition. Curr Drug Metab 13:1145–1159
  • Niwa T, Yasumura M, Murayama N, Yamazaki H. (2014). Comparison of catalytic properties of cytochromes P450 3A4 and 3A5 by molecular docking simulation. Drug Metab Lett 8:43–50
  • Ohmori S, Fujiki N, Nakasa H, et al. (1998). Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus. Res Commun Mol Pathol Pharmacol 100:15–28
  • Paracchini V, Pedotti P, Raimondi S, et al. (2005). A common CYP1B1 polymorphism is associated with 2-OHE1/16-OHE1 urinary estrone ratio. Clin Chem Lab Med 43:702–706
  • Papageorgiou I, Grepper S, Unadkat JD. (2013). Induction of hepatic CYP3A enzymes by pregnancy-related hormones: Studies in human hepatocytes and hepatic cell lines. Drug Metab Dispos 41:281–290
  • Peng CC, Templeton I, Thummel KE, et al. (2011). Evaluation of 6β-hydroxycortisol, 6β-hydroxycortisone, and a combination of the two as endogenous probes for inhibition of CYP3A4 in vivo. Clin Pharmacol Ther 89:888–895
  • Pikuleva IA. (2006a). Cytochrome P450s and cholesterol homeostasis. Pharmacol Ther 112:761–773
  • Pikuleva IA. (2006b). Cholesterol-metabolizing cytochromes P450. Drug Metab Dispos 34:513–520
  • Pikuleva IA, Waterman MR. (2013). Cytochromes p450: Roles in diseases. J Biol Chem 288:17091–17098
  • Rais N, Hussain A, Chawla YK, Kohli KK. (2013). Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population. Exp Ther Med 5:527–532
  • Rendic S. (2002). Summary of information on human CYP enzymes: Human P450 metabolism data. Drug Metab Rev 34:83–448
  • Rendic S, Di Carlo FJ. (1997). Human cytochrome P450 enzymes: A status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 29:413–580
  • Rendic S, Nolteernsting E, Schänzer W. (1999). Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes. Gas chromatographic-mass spectrometric determination of metabolites. J Chromatogr B Biomed Sci Appl 26: 73–83
  • Russo J, Hasan Lareef M, Balogh G, et al. (2003). Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells. J Steroid Biochem Mol Biol 87:1–25
  • Shackleton CH. (2012). Role of a disordered steroid metabolome in the elucidation of sterol and steroid biosynthesis. Lipids 47:1–12
  • Schwarz D, Kisselev P, Schunck WH, et al. (2000). Allelic variants of human cytochrome P450 1A1 (CYP1A1): Effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics 10:519–530
  • Shet MS, Fisher CW, Tremblay Y, et al. (2007). Comparison of the 17α-hydroxylase/C17,20-lyase activities of porcine, guinea pig and bovine P450c17 using purified recombinant fusion proteins containing P450c17 linked to NADPH-P450 reductase. Drug Metab Rev 39:289–307
  • Shimada T, Yamazaki H, Mimura M, et al. (1994). Interindividual variation in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270:414–423
  • Shimada T, Watanabe J, Kawajiri K, et al. (1999). Catalytic properties of polymorphic human cytochrome P450 1B1 variants. Carcinogenesis 20:1607–1613
  • Shinkyo R, Guengerich FP. (2011). Inhibition of human cytochrome P450 3A4 by cholesterol. J Biol Chem 286:18426–18433
  • 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
  • Spink DC, Spink BC, Cao JQ, et al. (1998). Differential expression of CYP1A1 and CYP1B1 in human breast epithelial cells and breast tumor cells. Carcinogenesis 19:291–298
  • Stevens JC, Hines RN, Gu C, et al. (2003). Developmental expression of the major human hepatic CYP3A enzymes. J Pharmacol Exp Ther 307:573–582
  • Storbeck KH, Swart P, Africander D, et al. (2011). 16α-Hydroxyprogesterone: Origin, biosynthesis and receptor interaction. Mol Cell Endocrinol 336:92–101
  • Sugimoto H, Shiro Y. (2012). Diversity and substrate specificity in the structures of steroidogenic cytochrome P450 enzymes. Biol Pharm Bull 35:818–823
  • Swinney DC. (1990). Progesterone metabolism in hepatic microsomes. Effect of the cytochrome P-450 inhibitor, ketoconazole, and the NADPH 5α-reductase inhibitor, 4-MA, upon the metabolic profile in human, monkey, dog, and rat. Drug Metab Dispos 18:859–865
  • Thomas JL, Duax WL, Addlagatta A, et al. (2003). Structure/function relationships responsible for coenzyme specificity and the isomerase activity of human type 1,3-β-hydroxysteroid dehydrogenase/isomerase. J Biol Chem 278:35483–35490
  • Usmani KA, Cho TM, Rose RL, Hodgson E. (2006). Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals. Drug Metab Dispos 34:1606–1614
  • Williams JA, Ring BJ, Cantrell VE, et al. (2002). Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos 30:883–891
  • Wu DA, Chung BC. (1991). Mutations of P450c21 (steroid 21-hydroxylase) at Cys428, Val281, and Ser268 result in complete, partial, or no loss of enzymatic activity, respectively. J Clin Invest 88:519–523
  • Yamazaki H, Nakamura M, Komatsu T, et al. (2002). Roles of NADPH-P450 reductase and apo- and holo-cytochrome b5 on xenobiotic oxidations catalyzed by 12 recombinant human cytochrome P450s expressed in membranes of Escherichia coli. Protein Expr Purif 24:329–337
  • Yamazaki H, Shaw PM, Guengerich FP, Shimada T. (1998). Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes. Chem Res Toxicol 11:659–665
  • Yamazaki H, Shimada T. (1997). Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys 346:161–169
  • Zhu BT, Conney AH. (1998). Functional role of estrogen metabolism in target cells: Review and perspectives. Carcinogenesis 19:1–27

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