The identification of nuclear receptors associated with hepatic steatosis to develop and extend adverse outcome pathways

References

• Adler S, Basketter D, Creton S, Pelkonen O, Benthem J, Valérie Zuang V, Andersen KE, et al. Alternative (non-animal) methods for cosmetics testing: current status and future prospects – 2010. Arch Toxicol 2011;85:367–485.
   PubMed Web of Science ®Google Scholar
• Alizadeh F, Bolhassani A, Khavari A, Bathaie SZ, Naji T, Bidgoli SA. Retinoids and their biological effects against cancer. Int Immunopharmacol 2014;18:43–49.
   PubMed Web of Science ®Google Scholar
• Al Sharif M, Alov P, Vitcheva V, Pajeva I, Tsakovska I. Modes-of-action related to repeated dose toxicity: from PPARgamma ligand-dependent dysregulation to non-alcoholic fatty liver disease. PPAR Research, Special issue, “PPARs and Metabolic Syndrome” 2014;2014:432647.
   Google Scholar
• Anbalagan M, Huderson B, Murphy L, Rowan BG. Post-translational modifications of nuclear receptors and human disease. Nucl Recept Signal 2012;10:e001.
   Google Scholar
• Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, et al. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem 2010;29:730–741.
   PubMed Web of Science ®Google Scholar
• AOP Wiki. The term hepatic steatosis has been searched for within the AOP wiki search function. Available from https://aopkb.org/aopwiki/index.php?search=hepatic+steatosis&title=Special%3ASearch&fulltext=Search (accessed on 26th April 2015).
   Google Scholar
• AOP wiki. NR linked to hepatic steatosis. Available from https://aopkb.org/aopwiki/index.php/Aop:34 (accessed on 5th May 2015).
   Google Scholar
• AOP-KB. The OECD webpage describing AOPs. Available from http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm (accessed on 26th April 2015).
   Google Scholar
• Apriletti JW, Ribeiro RC, Wagner RL, Feng W, Webb P, Kushner PJ, West BL, et al. Molecular and structural biology of thyroid hormone receptors. Clin Exp Pharmacol Physiol Suppl 1998;25:S2–S11.
   PubMedGoogle Scholar
• Arnett MG, Kolber BJ, Boyle MP, Muglia LJ. Behavioral insights from mouse models of forebrain- and amygdala-specific glucocorticoid receptor genetic disruption. Mol Cell Endocrinol 2011;336:2–5.
   PubMed Web of Science ®Google Scholar
• Azzout-Marniche D, Bécard D, Guichard C, Foretz M, Ferré P, Foufelle F. Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes. Biochem J 2000;350(Pt 2):389–393.
   PubMed Web of Science ®Google Scholar
• Baes M, Gulick T, Choi HS, Martinoli MG, Simha D, Moore DD. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response element. Mol Cell Biol 1994;14:1544–1552.
   PubMed Web of Science ®Google Scholar
• Bahn RS, Burch HS, Cooper DS, Garber JR, Greenlee CM, Klein IL, Laurberg P, et al. The role of propylthiouracil in the management of Graves’ disease in adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid 2009;19:673–674.
   PubMedGoogle Scholar
• Bandyopadhyay GK, Yu JG, Ofrecio J, Olefsky JM. Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis: thiazolidinedione treatment reverses these defects. Diabetes 2006;55:2277–2285.
   PubMed Web of Science ®Google Scholar
• Barral RL, Gold MA. Progestin-only contraception. Contraception for adolescent and young adult women. New York, USA: Springer; 2014. pp 25–44.
   Google Scholar
• Baulieu E, Schumacher M. Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination. Steroids 2000;65:605–612.
   PubMed Web of Science ®Google Scholar
• Bertilsson G, Heidrich J, Svensson K, Asman M, Jendeberg L, Sydow-Bäckman M, Ohlsson R, et al. Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction. Proc Natl Acad Sci USA 1998;95:12208–12213.
   PubMed Web of Science ®Google Scholar
• Biddie SC, Conway-Campbell BL, Lightman SL. Dynamic regulation of glucocorticoid signalling in health and disease. Rheumatology (Oxford) 2012;51:403–412.
   PubMed Web of Science ®Google Scholar
• Biesalski HK. Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology 1989;57:117–161.
   PubMed Web of Science ®Google Scholar
• Bitter A, Rümmele P, Klein K, Kandel BA, Rieger JK, Nüssler AK, Zanger UM, et al. Pregnane x receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms. Arch Toxicol 2014. [Epub ahead of print]. doi: 10.1007/s00204-014-1348-x.
   PubMed Web of Science ®Google Scholar
• Boverhof DR, Burgoon LD, Tashiro C, Sharratt B, Chittim B, Harkema JR, Mendrick DL, Zacharewski TR. Comparative toxicogenomic analysis of the hepatotoxic effects of TCDD in Sprague Dawley rats and C57BL/6 mice. Toxicol Sci 2006;94:398–416.
   PubMed Web of Science ®Google Scholar
• Bultink IE, Baden M, Lems WF. Glucocorticoid-induced osteoporosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother 2013;14:185–197.
   PubMed Web of Science ®Google Scholar
• Burden N, Sewell F, Andersen MF, Boobis A, Chipman JK, Cronin MTD, Hutchinson TH, et al. Adverse outcome pathways can drive non-animal approaches for safety assessment. J Appl Toxicol 2015;35:971–975.
   PubMed Web of Science ®Google Scholar
• Buttgereit F. A fresh look at glucocorticoids how to use an old ally more effectively. Bull NYU Hosp Jt Dis 2012;70(Suppl 1):26–29.
   PubMedGoogle Scholar
• Chambellan-Tison C, Horen B, Plat-Wilson G, Moulin P. Severe hypercalcemia due to vitamin D intoxication. Arch Pediatr 2007;14:1328–1332.
   PubMed Web of Science ®Google Scholar
• Cherrington NJ, Hartley DP, Li N, Johnson DR, Klaassen CD. Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats. J Pharmacol Exp Ther 2002;300:97–104.
   PubMed Web of Science ®Google Scholar
• Chourbaji S, Gass P. Glucocorticoid receptor transgenic mice as models for depression. Brain Res Rev 2008;57:554–560.
   PubMed Web of Science ®Google Scholar
• Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of pregnancy. N Engl J Med 2000;342:946–956.
   PubMed Web of Science ®Google Scholar
• Claudel T, Inoue Y, Barbier O, Duran-Sandoval D, Kosykh V, Fruchart J, Fruchart JC, et al. Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology 2003;125:544–555.
   PubMed Web of Science ®Google Scholar
• Claudel T, Staels B, Kuipers F. The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 2005;25:2020–2030.
   PubMed Web of Science ®Google Scholar
• Coenraads PJ. Hand eczema. N Engl J Med 2012;367:1829–1837.
   PubMed Web of Science ®Google Scholar
• Cohen Hubal EA, Richard A, Aylward L, Edwards S, Gallagher J, Goldsmith MR, Isukapalli S, et al. Advancing 1169 exposure characterization for chemical evaluation and risk assessment. J Toxicol Environ Health B Crit Rev 2010;13:299–313.
   PubMed Web of Science ®Google Scholar
• Couse JF, Korach KS. Estrogen receptor null mice: what have we learned and where will they lead us. Endocr Rev 1999;20:358–417.
   PubMed Web of Science ®Google Scholar
• Crescioli C. Vitamin D receptor agonists: suitable candidates as novel therapeutic options in autoimmune inflammatory myopathy. BioMed Res Int 2014;2014:10.
   Web of Science ®Google Scholar
• Cronin MTD, Livingston DJ. Predicting chemical toxicity and fate. New York, USA: CRC Press; 2004. pp 392–393.
   Google Scholar
• Dalakas MC. Immunotherapy of myositis: issues, concerns and future prospects. Nat Rev Rheumatol 2010;6:129–137.
   PubMed Web of Science ®Google Scholar
• DeManno D, Elger W, Garg R, Lee R, Schneider B, Hess-Stumpp H, Schubert G, Chwalisz K. Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy. Steroids 2003;68:1019–1032.
   PubMed Web of Science ®Google Scholar
• Dentin R, Denechaud PD, Benhamed F, Girard J, Postic C. Hepatic gene regulation by glucose and polyunsaturated fatty acids: a role for ChREBP. J Nutr 2006;136:1145–1149.
   PubMed Web of Science ®Google Scholar
• Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W. Control of the peroxisomal beta-oxidation pathway by a novel familyof nuclear hormone receptors. Cell 1992;68:879–887.
   PubMed Web of Science ®Google Scholar
• Edelman JL. Differentiating intraocular glucocorticoids. Ophthalmologica 2010;224(Suppl 1):25–30.
   PubMed Web of Science ®Google Scholar
• Elferink CJ, Gasiewicz TA, Whitlock JP Jr. Protein-DNA interactions at a dioxin-responsive enhancer. Evidence that the transformed Ah receptor is heteromeric. J Biol Chem 1990;265:20708–20712.
   PubMed Web of Science ®Google Scholar
• Engelken SF, Eaton RP. The effects of altered thyroid status on lipid metabolism in the genetic hyperlipemic Zucker rat. Atherosclerosis 1981:38:177–188.
   PubMed Web of Science ®Google Scholar
• Fardet L, Nazareth I. Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing’s syndrome: cohort study. BMJ 2012;345:e4928.
   PubMed Web of Science ®Google Scholar
• Foretz M, Guichard C, Ferre P, Foufelle F. Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expressionof glucokinase and lipogenesis-related genes. Proc Natl Acad Sci USA 1999;96:12737–12742.
   PubMed Web of Science ®Google Scholar
• Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, et al. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 1995;81:687–693.
   PubMed Web of Science ®Google Scholar
• Forrest D, Vennström B. Functions of thyroid hormone receptors in mice. Thyroid 2000;10:41–52.
   PubMed Web of Science ®Google Scholar
• Förster C, Mäkela S, Wärri A, Kietz S, Becker D, Hultenby K, Warner M, Gustafsson JÅ. Involvement of estrogen receptor β in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci USA 2002;99:15578–15583.
   PubMed Web of Science ®Google Scholar
• Foster DW. Malonyl-CoA: the regulator of fatty acid synthesis and oxidation. J Clin Investig 2012 122:1958–1959.
   PubMed Web of Science ®Google Scholar
• Gellersen B, Fernandes MS, Brosens JJ. Non-genomic progesterone actions in female reproduction. Hum Reprod Update 2009;151:119–138.
   Google Scholar
• Gelmann EP. Molecular biology of the androgen receptor. J Clin Oncol 2002;20:3001–3015.
   PubMed Web of Science ®Google Scholar
• Gizzo S, Andrisani A, Esposito F, Noventa M, Di Gangi S, Angioni S, Litta P, et al. Which luteal phase support is better for each IVF stimulation protocol to achieve the highest pregnancy rate? A superiority randomized clinical trial. Gynecol Endocrinol 2014;1–7:Early Online.
   PubMedGoogle Scholar
• Gocht T, Berggren E, Ahr HJ, Cotgreave I, Cronin MTD, Daston G, Hardy B, et al. The SEURAT-1 approach towards animal free human safety assessment. ALTEX 2015;32:9–24.
   PubMedGoogle Scholar
• Gonzalez FJ, Gelboin HV. Human cytochromes P450: evolution, catalytic activities and interindividual variations in expression. Prog Clin Biol Res 1991;372:11–20.
   PubMedGoogle Scholar
• Gougelet A, Bouclier C, Marsaud V, Maillard S, Mueller SO, Korach KS, Renoir JM. Estrogen receptor α and β subtype expression and transactivation capacity are differentially affected by receptor-, hsp90- and immunophilin-ligands in human breast cancer cells. J Steroid Biochem Mol Biol 2005;94:71–81.
   PubMed Web of Science ®Google Scholar
• Grefhorst A, Elzinga BM, Voshol PJ, Plösch T, Kok T, Bloks VW, van der Sluijs FH, et al. Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J Biol Chem 2002;277:34182–34190.
   PubMed Web of Science ®Google Scholar
• Groh KJ, Carvalho RN, Chipman JK, Denslow ND, Halder M, Murphy CA, Roelofs D, et al. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: I. Challenges and research needs in ecotoxicology. Chemosphere 2015;120:764–777.
   PubMed Web of Science ®Google Scholar
• Gustafsson JA. What pharmacologists can learn from recent advances in estrogen signalling. Trends Pharmacol Sci 2003;24:479–485.
   PubMed Web of Science ®Google Scholar
• Haas DM, Ramsey PS. Progestogen for preventing miscarriage. Cochrane Database Syst Rev 2013;(13):CD003511. doi: 10.1002/14651858.CD003511.pub3.
   Google Scholar
• Hakim A, Adcock IM, Usmani OS. Corticosteroid resistance and novel anti-inflammatory therapies in chronic obstructive pulmonary disease: current evidence and future direction. Drugs 2012;72:1299–1312.
   PubMed Web of Science ®Google Scholar
• Hansson P, Valdemarsson S, Nilsson-Ehle P. Experimental hyperthyroidism in man: effects on plasma lipoproteins, lipoprotein lipase and hepatic lipase. Horm Metab Res 1983;15:449–452.
   PubMed Web of Science ®Google Scholar
• Harris WP, Mostaghel EA, Nelson PS, Montgomery B. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion. Natl Clin Pract Urol 2009;6:76–85.
   PubMedGoogle Scholar
• Hartung, T, McBride M. Food for thought on mapping the human toxome. ALTEX 2011;28:83–93.
   PubMedGoogle Scholar
• Hashimoto T, Fujita T, Usuda N, Cook W, Qi C, Peters JM, Gonzalez FJ, et al. Peroxisomal and mitochondrial fatty acid β-oxidation in mice nullizygous for both peroxisome proliferator-activated receptor α and peroxisomal fatty acyl-CoA oxidase. J Biol Chem 1999;274:19228–19236.
   PubMed Web of Science ®Google Scholar
• Haussler MR, Haussler CA, Bartik L, Whitfield GK, Hsieh J, Slater S, Jurutka PW. Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention. Nutr Rev 2008;66(Suppl 2):S98–S112.
   PubMed Web of Science ®Google Scholar
• He J, Lee JH, Febbraio, Xie W. The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver disease. Exp Biol Med 2011;236:1116–1121.
   Web of Science ®Google Scholar
• Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, Tujague M, et al. Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007;87:905–931.
   PubMed Web of Science ®Google Scholar
• Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, Thaller C. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell 1992;68:397–406.
   PubMed Web of Science ®Google Scholar
• Hoekstra M, Lammers B, Out R, Li Z, Van Eck M, Van Berkel TJ. Activation of the nuclear receptor PXR decreases plasma LDL-cholesterol levels and induces hepatic steatosis in LDL receptor knockout mice. Mol Pharm 2009;6:182–189.
   PubMed Web of Science ®Google Scholar
• Honkakoski P, Moore R, Washburn K, Negishi M. Activation by diverse xenochemicals of the 51-base pair phenobarbital-responsive enhancer module in the CYP2B10 gene. Mol Pharmacol 1998;53:597–601.
   PubMed Web of Science ®Google Scholar
• Horwitz KB, Tung L, Takimoto GS. Progestins, progesterone receptors and breast cancer. In: Vedeckis WV, editor. Hormones and cancer. Boston: Birkhaeuser; 1996. pp 283–306.
   Google Scholar
• Howard WR, Pospisil JA, Njolito E, Noonan DJ. Catabolites of cholesterol synthesis pathways and forskolin as activators of the farnesoid X-activated nuclear receptor. Toxicol Appl Pharmacol 2000;163:195–202.
   PubMed Web of Science ®Google Scholar
• Huang W, Zhang J, Moore DD. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest 2004;113:137–143.
   PubMed Web of Science ®Google Scholar
• Ihunnah CA, Jiang M, Xie W. Nuclear receptor PXR, transcriptional circuits and metabolic relevance. Biochim Biophys Acta 2011;1812:956–963.
   PubMed Web of Science ®Google Scholar
• Iser JH, Dowling H, Mok HY, Bell GD. Chenodeoxycholic acid treatment of gallstones. A follow-up report and analysis of factors influencing response to therapy. N Engl J Med 1975;293:378–383.
   PubMed Web of Science ®Google Scholar
• Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990;347:645–650.
   PubMed Web of Science ®Google Scholar
• Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 1996;383:728–731.
   PubMed Web of Science ®Google Scholar
• Jia Y, Viswakarma N, Fu T, Yu S, Rao MS, Borensztajn J, Reddy JK. Conditional ablation of mediator subunit MED1 (MED1/PPARBP) gene in mouse liver attenuates glucocorticoid receptor agonist dexamethasone-induced hepatic steatosis. Gene Exp 2009;14:291–306.
   Google Scholar
• Jung UJ, Millman PN, Tall AR, Deckelbaum RJ. n −3 Fatty acids ameliorate hepatic steatosis and dysfunction after LXR agonist ingestion in mice. Biochim Biophys Acta 2011;1811:491–497.
   PubMed Web of Science ®Google Scholar
• Karas RH, Eickels MV, Lydon JP, Roddy S, Kwoun M, Aronovitz M, Baur WE, et al. A complex role for the progesterone receptor in the response to vascular injury. J Clin Invest 2001;108:611–618.
   PubMed Web of Science ®Google Scholar
• Kasimanickam VR, Kasimanickam RK, Rogers HA. Immunolocalization of retinoic acid receptor-alpha, -beta, and -gamma, in bovine and canine sperm. Theriogenology 2013;79:1010–1018.
   PubMed Web of Science ®Google Scholar
• Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, et al. Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem 2002;277:2908–2915.
   PubMed Web of Science ®Google Scholar
• Kawaguchi M, Mitsuhashi Y, Kondo SJ. Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24(OH)2D3) combined with thiazide diuretics in a case of psoriasis. Dermatology 2003;30:801–804.
   Web of Science ®Google Scholar
• Kawano Y, Nishiumi S, Tanaka S, Nobutani K, Miki A, Yano Y, Seo Y, et al. Activation of the aryl hydrocarbon receptor induces hepatic steatosis via the upregulation of fatty acid transport. Arch Biochem Biophys 2010;504:221–227.
   PubMed Web of Science ®Google Scholar
• Kettel LM, Murphy AA, Mortola JF, Liu JH, Ulmann A, Yen SS. Induction of abortion with mifepristone and misoprostol in early pregnancy. Fertil Steril Br J Obstet Gynaecol 1992;99:1004–1007.
   PubMed Web of Science ®Google Scholar
• Kiernan DF, Mieler WF. The use of intraocular corticosteroids. Expert Opin Pharmacother 2009;10:2511–2525.
   PubMed Web of Science ®Google Scholar
• King TL, Brucker MC. Pharmacology for women’s health. Burlington, USA: Jones & Bartlett Publishers; 2010. pp 372–373.
   Google Scholar
• Kliewer SA, Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf DJ, Umesono K, Evans RM. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 1994;91:7355–7359.
   PubMed Web of Science ®Google Scholar
• Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA, McKee DD, et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 1998;92:73–82.
   PubMed Web of Science ®Google Scholar
• Kuiper GG, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 1997;138:863–870.
   PubMed Web of Science ®Google Scholar
• Laffitte BA, Kast HR, Nguyen CM, Zavacki AM, Moore DD, Edwards PA. Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J Biol Chem 2000;275:10638–10647.
   PubMed Web of Science ®Google Scholar
• Lazar MA. (1993). Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev 1993;14:184–193.
   Google Scholar
• Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM, et al. Targeted disruption of the alpha isoform of the peroxisome proliferator-activatedreceptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 1995;15:3012–3022.
   PubMed Web of Science ®Google Scholar
• Lelliott CJ, López M, Curtis RK, Parker N, Laudes M, Yeo G, Jimenez-Liñan M, et al. Transcript and metabolite analysis of the effects of tamoxifen in rat liver reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis. FASEB J 2005;19:1108–1119.
   PubMed Web of Science ®Google Scholar
• Letteron P, Brahimi-Bourouina N, Robin M-A, Moreau A, Feldman G, Pessayre D. Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty acid β-oxidation. Am J Physiol Gastrointest Liver Physiol 1997;272:G1141–G1150.
   PubMed Web of Science ®Google Scholar
• Lewis-Tuffin LJ, Jewell CM, Bienstock RJ, Collins JB, Cidlowski JA. Human glucocorticoid receptor beta binds RU-486 and is transcriptionally active. Mol Cell Biol 2007;27:2266–2282.
   PubMed Web of Science ®Google Scholar
• Leyden JJ, Shalita A, Thiboutot D, Washenik K, Webster G. Topical retinoids in inflammatory acne: a retrospective, investigator-blinded, vehicle-controlled, photographic assessment. Clin Ther 2005;27:216–224.
   PubMed Web of Science ®Google Scholar
• Li T, Yu RT, Atkins AR, Downes M, Tukey RH, Evans RM. Targeting the pregnane X receptor in liver injury. Expert Opin Ther Targets 2012;16:1075–1083.
   PubMed Web of Science ®Google Scholar
• Li W, Donat S, Dohr O, Unfried K, Abel J. Ah receptor in different tissues of C57BL/6J and DBA/2J mice: use of competitive polymerase chain reaction to measure Ah-receptor mRNA expression. Arch Biochem Biophys 1994;315:279–284.
   PubMed Web of Science ®Google Scholar
• Lin JZ, Martagón AJ, Hsueh WA, Baxter JD, Gustafsson JÅ, Webb P, Phillips KJ. Thyroid hormone receptor agonists reduce serum cholesterol independent of the LDL receptor. Endocrinology 2012;153:6136–6144.
   PubMed Web of Science ®Google Scholar
• Liu Z, Hu Q, Rosenfeld MG. Complexity of the RAR-mediated transcriptional regulatory programs. Subcell Biochem 2014;70:203–225.
   PubMedGoogle Scholar
• Loireau A, Autissier N, Dumas P, Michael O, Jorgensen EC, Michael R. Comparative effects of 3,5-dimethyl-3’-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3’-isopropylthyroacetic acid (IpTA2) on body weight gain and lipid metabolism ingenetically obese Zucker rats. Biochem Pharmacol 1986;35:1691–1696.
   PubMed Web of Science ®Google Scholar
• Love JD. Nuclear receptors and disease. John Wiley & Sons. eLS 2006. DOI: 10.1038/npg.els.0006024.
   Google Scholar
• Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, et al. International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev 2006;58:782–797.
   PubMed Web of Science ®Google Scholar
• Ma WL, Lai HC, Yeh S, Cai X, Chang C. Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis. Endocrine-related cancer 2014;21:R165–R182.
   Google Scholar
• Maglich JM, Lobe DC, Moore JT. The nuclear receptor CAR (NR1I3) regulates serum triglyceride levels under conditions of metabolic stress. J Lipid Res 2009;50:439–445.
   PubMed Web of Science ®Google Scholar
• Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, et al. Identification of a nuclear receptor for bile acids. Science 1999;284:1362–1365.
   PubMed Web of Science ®Google Scholar
• Miquilena-Colina ME, Lima-Cabello E, Sanchez-Campos S, Garcıa-Mediavilla MV, Fernandez-Bermejo M, Lozano-Rodrıguez T, Vargas-Castrillon J, et al. Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C. Gut 2011;60:1394–1402.
   PubMed Web of Science ®Google Scholar
• Misrahi M, Atger M, d’Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, et al. Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem Biophys Res Commun 1987;143:740–748.
   PubMed Web of Science ®Google Scholar
• Morani ABR, Imamov O, Hultenby K, Arner A, Warner M, Gustafsson JA. Lung dysfunction causes systemic hypoxia in estrogen receptor beta knockout (ERbeta−/−) mice. Proc Natl Acad Sci USA 2006;103:7165–7169.
   PubMed Web of Science ®Google Scholar
• Moreau A, Vilarem MJ, Maurel P, Pascussi JM. CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 2008;5:35–41.
   PubMed Web of Science ®Google Scholar
• Moya M, Gómez-Lechón MJ, Castell JV, Jover R. Enhanced steatosis by nuclear receptor ligands: a study in cultured human hepatocytes and hepatoma cells with a characterized nuclear receptor expression profile. Chem Biol Interact 2010;184:376–387.
   PubMed Web of Science ®Google Scholar
• Murphy AA, Kettel LM, Morales AJ, Roberts VJ, Yen SS. Regression of uterine leiomyomata in response to the antiprogesterone RU 486. J Clin Endocrinol Metab 1993;76:513–517.
   PubMed Web of Science ®Google Scholar
• Nguyen P, Leray V, Diez M, Serisier S, Le Bloch J, Dumon H. Liver lipid metabolism. J Anim Physiol Anim Nutr 2008;92:272–283.
   PubMed Web of Science ®Google Scholar
• Naik MA, Banday KA, Najar MS, Reshi AR, Bhat MA. Vitamin D intoxication presenting as acute renal failure. Indian J Nephrol 2008;18:125–126.
   PubMedGoogle Scholar
• National Research Council (NRC). Toxicity testing in the 21st century: a 1321 vision and a strategy. Washington, DC: National Academies Press; 2007.
   Google Scholar
• Nebert DW, Dalton TP, Okey AB, Gonzalez FJ. Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 2004;279:23847–23850.
   PubMed Web of Science ®Google Scholar
• Niittynen M, Simanainen U, Syrjälä P, Pohjanvirta R, Viluksela M, Tuomisto J, Tuomisto JT. Differences in acute toxicity syndromes of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin in rats. Toxicology 2007;235:39–51.
   PubMed Web of Science ®Google Scholar
• Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology 2006;147:5542–5548.
   PubMed Web of Science ®Google Scholar
• O’Bryant CL, Flaig TW, Utz KJ. Bicalutamide-associated fulminant hepatotoxicity. Pharmacotherapy 2008;28:1071–1075.
   PubMed Web of Science ®Google Scholar
• Osabe M, Sugatani J, Fukuyama T, Ikushiro S, Ikari A, Miwa M. Expression of hepatic UDP-glucuronosyltransferase 1A1 and 1A6 correlated with increased expression of the nuclear constitutive androstane receptor and peroxisome proliferator-activated receptor alpha in male rats fed a high-fat and highsucrose diet. Drug Metab Dispos 2008;36:294–302.
   PubMed Web of Science ®Google Scholar
• Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, et al. Bile acids: natural ligands for an orphan nuclear receptor. Science 1999;284:1365–1368.
   PubMed Web of Science ®Google Scholar
• Patlewicz G, Simon T, Rowlands JC, Budinsky RA, Becker RA. Proposing a scientific confidence framework to help support the application of adverse outcome pathways for regulatory purposes. Regul Toxicol Pharmacol 2015;71:463–477.
   PubMed Web of Science ®Google Scholar
• Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, Mangelsdorf DJ. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 1998;93:693–704.
   PubMed Web of Science ®Google Scholar
• Pelclová D, Urban P, Preiss J, Lukás E, Fenclová Z, Navrátil T, Dubská Z, Senholdová Z. Adverse health effects in humans exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rev Environ Health 2006;21:119–138.
   PubMedGoogle Scholar
• Peraza MA, Burdick AD, Marin HE, Gonzalez FJ, Peters JM. The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR). Toxicol Sci 2006;90:269–295.
   PubMed Web of Science ®Google Scholar
• Pérez E, Bourguet W, Gronemeyer H, de Lera AR. Modulation of RXR function through ligand design. Biochim Biophys Acta 2012;1821:57–69.
   PubMed Web of Science ®Google Scholar
• Peters JM, Cheung C, Gonzalez FJ. Peroxisome proliferator activated receptor-alpha and liver cancer: where do we stand? J Mol Med 2005;83:774–785.
   PubMed Web of Science ®Google Scholar
• Peters JM, Hennuyer N, Staels B, Fruchart JC, Fievet C, Gonzalez FJ, Auwerx J. Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice. J Biol Chem 1997;272:27307–27312.
   PubMed Web of Science ®Google Scholar
• Petitti DB. Combination estrogen–progestin oral contraceptives. N Engl J Med 2003;349:1443–1450.
   PubMed Web of Science ®Google Scholar
• Pineda Torra I, Claudel T, Duval C, Kosykh V, Fruchart JC, Staels B. Bile acids induce the expression of the human peroxisome proliferator-activated receptor α gene via activation of the farnesoid X receptor. Mol Endocrinol 2003;17:259–272.
   PubMed Web of Science ®Google Scholar
• Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008;118:829–838.
   PubMed Web of Science ®Google Scholar
• Raparti G, Jain S, Ramteke K, Murthy M, Ghanghas R, Ramanand S, Ramanand J. Selective thyroid hormone receptor modulators. Indian J Endocrinol Metab 2013;17: 211–218.
   PubMedGoogle Scholar
• Reddy JK, Roa SM. Lipid metabolism and liver inflammation II. Fatty liver disease and fatty oxidation. Am J Physiol Gastrointest Liver Physiol 2006;290:G853–G858.
   Google Scholar
• Repa JJ, Berge KE, Pomajzl C, Richardson JA, Hobbs H, Mangelsdorf DJ. Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta. J Biol Chem 2002;277:18793–18800.
   PubMed Web of Science ®Google Scholar
• Repa JJ, Turley SD, Lobaccaro JA, Medina J, Li L, Lustig K, Shan B, et al. Regulation of absorption and ABC1-mediated Efflux of cholesterol by RXR heterodimers. Science 2000;289:1524–1529.
   PubMed Web of Science ®Google Scholar
• Rosano GMC, Fini M. Comparative cardiovascular effects of different progestins in menopause. Int J Fertil Womens Med 2001;46:248–256.
   PubMed Web of Science ®Google Scholar
• Rose AJ, Vegiopoulos A, Herzig S. Role of glucocorticoids and the glucocorticoid receptor in metabolism: insights from genetic manipulations. J Steroid Biochem Mol Biol 2010;122:10–20.
   PubMed Web of Science ®Google Scholar
• Rosen MB, Abbott BD, Wolf DC, Corton JC, Wood CR, Schmid JE, Das KP, et al. Gene profiling in the livers of wild-type and PPARalpha-null mice exposed to perfluorooctanoic acid. Toxicol Pathol 2008;36:592–607.
   PubMed Web of Science ®Google Scholar
• Rossier MF. T channels and steroid biosynthesis: in search of a link with mitochondria. Cell Calcium 2006;40:155–164.
   PubMed Web of Science ®Google Scholar
• Roy AK, Lavrovsky Y, Song CS, Chen S, Jung MH, Velu NK, Bi BY, Chatterjee B. Regulation of androgen action. Vitam Horm 1999;55:309–352.
   PubMed Web of Science ®Google Scholar
• Saini SP, Sonoda J, Xu L, Toma D, Uppal H, Mu Y, Ren S, et al. A novel constitutive andros-tane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol 2004;65:292–300.
   PubMed Web of Science ®Google Scholar
• Satoh H, Ide N, Kagawa Y, Maeda T. Hepatic steatosis with relation to increased expression of peroxisome proliferator-activated receptor-γ in insulin resistant mice. Biol Pharm Bull 2013;36:616–623.
   PubMed Web of Science ®Google Scholar
• Schultz JR, Tu H, Luk A, Pepa JJ, Medina JC, Li L, Schwendner S, et al. Role of LXRs in control of lipogenesis. Genes Dev 2000;14:2831–2838.
   PubMed Web of Science ®Google Scholar
• Sevilla LM, Latorre V, Sanchis A, Pérez P. Epidermal inactivation of the glucocorticoid receptor triggers skin barrier defects and cutaneous inflammation. J Invest Dermatol 2012;133:361–370.
   PubMed Web of Science ®Google Scholar
• Shalita AR. Lipid and teratogenic effects of retinoids. J Am Acad Dermatol 1988;19:197–198.
   PubMed Web of Science ®Google Scholar
• Shimizu T, Yu HP, Hsieh YC, Choudhry MA, Suzuki T, Bland KI, Chaudry IH. Flutamide attenuates pro-inflammatory cytokine production and hepatic injury following trauma-hemorrhage via estrogen receptor-related pathway. Ann Surg 2007;245:297–304.
   PubMed Web of Science ®Google Scholar
• Silverman MN, Sternberg EM. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction. Ann NY Acad Sci 2012;1261:55–63.
   PubMed Web of Science ®Google Scholar
• Singer EA, Srinivasan R. Intravenous therapies for castration-resistant prostate cancer: toxicities and adverse events. Urol Oncol 2012;30:S15–S19.
   PubMed Web of Science ®Google Scholar
• Sitruk-Ware R, Spitz IM. Pharmacological properties of mifepristone: toxicology and safety in animal and human studies. Contraception 2003;68:409–420.
   PubMed Web of Science ®Google Scholar
• Skouby SO, Petersen KR. Clinical experience with the recently developed progestogens. Int J Fertility 1991,36(Suppl 1):32–37.
   PubMedGoogle Scholar
• Smith G, Henderson CJ, Parker MG, White R, Bars RG, Wolf CR. 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene, an extremely potent modulator of mouse hepatic cytochrome P-450 gene expression. Biochem J 1993;289:807–813.
   PubMed Web of Science ®Google Scholar
• Spitz IM. Progesterone receptor antagonists. Curr Opin Investig Drugs 2006;7:882–890.
   PubMed Web of Science ®Google Scholar
• Sueyoshi T, Kawamoto T, Zelko I, Honkakoski P, Negishi M. The repressed nuclear receptor CAR responds to phenobar-bital in activating the human CYP2B6 gene. J Biol Chem 1999;274:6043–6046.
   PubMed Web of Science ®Google Scholar
• Sugatani J, Kojima H, Ueda A, Kakizaki S, Yoshinari K, Gong QH, Owens IS, et al. The phenobar-bital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology 2001;33:1232–1238.
   PubMed Web of Science ®Google Scholar
• Suino K, Peng L, Reynolds R, Li Y, Cha JY, Repa JJ, Kliewer SA, Xu HE. The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization. Molecular Cell 2004;16:893–905.
   PubMed Web of Science ®Google Scholar
• Takeda K, Sakurai A, DeGroot LJ, Refetoff S. Recessive inheritance of thyroid hormone resistance caused by complete deletion of the protein-coding region of the thyroid hormone receptor-â gene. J Clin Endocrin Metab 1992;74:49–55.
   PubMed Web of Science ®Google Scholar
• Thomin A, Keller V, Daraï E, Chabbert-Buffet N. Consequences of emergency contraceptives: the adverse effects. Expert Opin Drug Saf 2014;13:893–902.
   Google Scholar
• Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban PC, Bock R, et al. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 1999;23:99–103.
   PubMed Web of Science ®Google Scholar
• Vatner DF, Weismann D, Beddow SA, Kumashiro N, Erion DM, Liao X, Grover GJ, et al. Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways. Am J Physiol Endocrinol Metab 2013;305:89–100.
   PubMed Web of Science ®Google Scholar
• Venkatesh M, Wang H, Cayer J, Leroux M, Salvail D, Das B, Wrobel JE, Mani S. In vivo and in vitro characterization of a first-in-class novel azole analog that targets pregnane X receptor activation. Mol Pharmacol 2011;80:124–135.
   PubMed Web of Science ®Google Scholar
• Vilasco M, Communal L, Mourra N, Courtin A, Forgez P, Gompel A. Glucocorticoid receptor and breast cancer. Breast Cancer Res Treat 2011;130:1–10.
   PubMed Web of Science ®Google Scholar
• Vinken M. The adverse outcome pathway concept: a pragmatic tool in toxicology. Toxicology 2013;312:158–165.
   PubMed Web of Science ®Google Scholar
• Vinken M. Adverse outcome pathways and drug-induced liver injury. Chem Res Toxicol 2015;28:1391–1397.
   PubMed Web of Science ®Google Scholar
• Wada T, Gao J, Xie W PXR and CAR in energy metabolism. Trends Endocrinol Metab 2009;20:273–279.
   PubMed Web of Science ®Google Scholar
• Wang L, Andersson S, Warner M, Gustafsson JA. Morphological abnormalities in the brains of estrogen receptor beta knockout mice. Proc Natl Acad Sci USA 2001;98:2792–2796.
   PubMed Web of Science ®Google Scholar
• Watkins RE, Wisely GB, Moore LB, Collins JL, Lambert MH, Williams SP, Willson TM, et al. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science 2001;292:2329–2333.
   PubMed Web of Science ®Google Scholar
• Waxman DJ. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 1999;369:11–23.
   PubMed Web of Science ®Google Scholar
• Weihua Z, Makela S, Andersson LC, Salmi S, Saji S, Webster JI, Jensen EV, et al. A role for estrogen receptor beta in the regulation of growth of the ventral prostate. Proc Natl Acad Sci USA 2001;98:6330–6335.
   PubMed Web of Science ®Google Scholar
• Weinstein RS, Wan C, Liu Q, Wang Y, Almeida M, O’Brien CA, Thostenson J, et al. Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice. Aging Cell 2010;9:147–161.
   PubMed Web of Science ®Google Scholar
• Wellington K, Perry CM. Estradiol valerate/dienogest. Drugs 2002;62:491–450.
   PubMed Web of Science ®Google Scholar
• Xie W, Barwick JL, Downes M, et al. Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 2000;406:435–439.
   PubMed Web of Science ®Google Scholar
• Xie W, Yeuh MF, Radominska-Pandya A, Saini SP, Negishi Y, Bottroff BS, Cabrera GY, et al. Control of steroid, heme, and carcinogen metabolism by nuclear preg-nane X receptor and constitutive androstane receptor. Proc Natl Acad Sci USA 2003;100:4150–4155.
   PubMed Web of Science ®Google Scholar
• Yaghmaei S, Roberts C, Ai R, Mizwicki MT, Chang CA. Agonist and antagonist binding to the nuclear vitamin D receptor: dynamics, mutation effects and functional implications. In Silico Pharmacol 2013;1:2. doi: 10.1186/2193-9616-1-2.
   PubMedGoogle Scholar
• Yamamoto Y, Moore R, Goldsworthy TL, Negishi M, Maronpot RR. The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. Cancer Res 2004;64:7197–7200.
   PubMed Web of Science ®Google Scholar
• Ye L, Li YL, Mellström K, Mellin C, Bladh LG, Koehler K, Garg N, et al. Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1. Med Chem 2003;46:1580–1588.
   Web of Science ®Google Scholar
• Yin Y, Yu Z, Xia M, Luo X, Lu X, Ling W. Vitamin D attenuates high fat diet-induced hepatic steatosis in rats by modulating lipid metabolism. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China. Eur J Clin Investig 2012;42:1189–1196.
   PubMed Web of Science ®Google Scholar
• Zafrani E. Non-alcoholic fatty liver disease: an emerging pathological spectrum. Virchows Arch 2004;444:3–12.
   PubMed Web of Science ®Google Scholar
• Zaghini I, Landrier JF, Grober J, Krief S, Jones SA, Monnot MC, Lefrère I, et al. Sterol regulatory element-binding protein-1c is responsible for cholesterol regulation of ileal bile acid-binding protein gene in vivo. Possible involvement of liver-X-receptor. J Biol Chem 2002;277:1324–1331.
   PubMed Web of Science ®Google Scholar
• Zambrana J, Zambrana F, Neto F, Gonçalves A, Zambrana F, Ushirohira J. Agranulocytosis with tonsillitis associated with methimazole therapy. Braz J Otorhinolaryngol 2005;71:374–377.
   PubMedGoogle Scholar
• Zen M, Canova M, Campana C, Bettio S, Nalotto L, Rampudda M, Ramonda R, et al. The kaleidoscope of glucocorticoid effects on immune system. Autoimmun Rev 2011;10:305–310.
   PubMed Web of Science ®Google Scholar
• Zhang L, Ge L, Parimoo S, Stenn K, Prouty SM. Human stearoyl-CoA desaturase: alternative transcripts generated from a single gene by usage of tandem polyadenylation sites. Biochem J 1999;340(Pt 1):255–264.
   PubMed Web of Science ®Google Scholar
• Zhao A, Yu J, Lew JL, Huang L, Wright SD, Cui J. Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. DNA Cell Biol 2004;23:519–526.
   PubMed Web of Science ®Google Scholar