{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T03:00:03Z","timestamp":1768273203978,"version":"3.49.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["602156"],"award-info":[{"award-number":["602156"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/01089"],"award-info":[{"award-number":["PI17\/01089"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CD18\/00158"],"award-info":[{"award-number":["CD18\/00158"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1007\/s00204-019-02643-y","type":"journal-article","created":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T09:02:37Z","timestamp":1577869357000},"page":"589-607","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Epistane, an anabolic steroid used for recreational purposes, causes cholestasis with elevated levels of cholic acid conjugates, by upregulating bile acid synthesis (CYP8B1) and cross-talking with nuclear receptors in human hepatocytes"],"prefix":"10.1007","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9697-4317","authenticated-orcid":false,"given":"Petar D.","family":"Petrov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-9834","authenticated-orcid":false,"given":"Leonor","family":"Fern\u00e1ndez-Murga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Conde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Mart\u00ednez-Sena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Guzm\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1179-6430","authenticated-orcid":false,"given":"Jos\u00e9 Vicente","family":"Castell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4914-5804","authenticated-orcid":false,"given":"Ramiro","family":"Jover","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2643_CR1","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.amjcard.2010.05.013","volume":"106","author":"S Achar","year":"2010","unstructured":"Achar S, Rostamian A, Narayan SM (2010) Cardiac and metabolic effects of anabolic-androgenic steroid abuse on lipids, blood pressure, left ventricular dimensions, and rhythm. Am J Cardiol 106:893\u2013901","journal-title":"Am J Cardiol"},{"key":"2643_CR2","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1021\/ac102845y","volume":"83","author":"ON Akram","year":"2011","unstructured":"Akram ON, Bursill C, Desai R et al (2011) Evaluation of androgenic activity of nutraceutical-derived steroids using mammalian and yeast in vitro androgen bioassays. Anal Chem 83:2065\u20132074. https:\/\/doi.org\/10.1021\/ac102845y","journal-title":"Anal Chem"},{"key":"2643_CR3","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3109\/00498254.2014.955831","volume":"45","author":"L Badolo","year":"2015","unstructured":"Badolo L, Jensen B, S\u00e4ll C et al (2015) Evaluation of 309 molecules as inducers of CYP3A4, CYP2B6, CYP1A2, OATP1B1, OCT1, MDR1, MRP2, MRP3 and BCRP in cryopreserved human hepatocytes in sandwich culture. Xenobiotica 45:177\u2013187. https:\/\/doi.org\/10.3109\/00498254.2014.955831","journal-title":"Xenobiotica"},{"key":"2643_CR4","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.mam.2013.12.001","volume":"37","author":"A Baghdasaryan","year":"2014","unstructured":"Baghdasaryan A, Chiba P, Trauner M (2014) Clinical application of transcriptional activators of bile salt transporters. Mol Asp Med 37:57\u201376","journal-title":"Mol Asp Med"},{"key":"2643_CR5","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.2741\/3416","volume":"14","author":"N Ballatori","year":"2009","unstructured":"Ballatori N, Li N, Fang F et al (2009) OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids. Front Biosci 14:2829\u20132844. https:\/\/doi.org\/10.2741\/3416","journal-title":"Front Biosci"},{"key":"2643_CR6","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1101\/gad.1564207","volume":"21","author":"EC Bolton","year":"2007","unstructured":"Bolton EC, So AY, Chaivorapol C et al (2007) Cell- and gene-specific regulation of primary target genes by the androgen receptor. Genes Dev 21:2005\u20132017. https:\/\/doi.org\/10.1101\/gad.1564207","journal-title":"Genes Dev"},{"key":"2643_CR7","doi-asserted-by":"publisher","first-page":"G1124","DOI":"10.1152\/ajpgi.00539.2005","volume":"290","author":"JL Boyer","year":"2006","unstructured":"Boyer JL, Trauner M, Mennone A et al (2006) Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents. Am J Physiol Gastrointest Liver Physiol 290:G1124\u2013G1130. https:\/\/doi.org\/10.1152\/ajpgi.00539.2005","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2643_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S0168-8278(98)80207-9","volume":"28","author":"D Brites","year":"1998","unstructured":"Brites D, Rodrigues CMP, Oliveira N et al (1998) Correction of maternal serum bile acid profile during ursodeoxycholic acid therapy in cholestasis of pregnancy. J Hepatol 28:91\u201398. https:\/\/doi.org\/10.1016\/S0168-8278(98)80207-9","journal-title":"J Hepatol"},{"key":"2643_CR9","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nrm3312","volume":"13","author":"AC Calkin","year":"2012","unstructured":"Calkin AC, Tontonoz P (2012) Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nat Rev Mol Cell Biol 13:213\u2013224","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2643_CR10","doi-asserted-by":"publisher","DOI":"10.1210\/me.2015-1014","author":"Y Chen","year":"2015","unstructured":"Chen Y, Vasilenko A, Song X et al (2015) Estrogen and estrogen receptor-\u03b1-mediated transrepression of bile salt export pump. Mol Endocrinol. https:\/\/doi.org\/10.1210\/me.2015-1014","journal-title":"Mol Endocrinol"},{"key":"2643_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2016.01.009","author":"Y Cherkas","year":"2016","unstructured":"Cherkas Y, McMillian MK, Amaratunga D et al (2016) ABC gene-ranking for prediction of drug-induced cholestasis in rats. Toxicol Rep. https:\/\/doi.org\/10.1016\/j.toxrep.2016.01.009","journal-title":"Toxicol Rep"},{"key":"2643_CR12","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201701084RR","author":"R Chevre","year":"2018","unstructured":"Chevre R, Trigueros-Motos L, Casta\u00f1o D et al (2018) Therapeutic modulation of the bile acid pool by cyp8b1 knockdown protects against nonalcoholic fatty liver disease in mice. FASEB J. https:\/\/doi.org\/10.1096\/fj.201701084RR","journal-title":"FASEB J"},{"key":"2643_CR13","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.jhep.2003.11.006","volume":"40","author":"JYL Chiang","year":"2004","unstructured":"Chiang JYL (2004) Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J Hepatol 40:539\u2013551","journal-title":"J Hepatol"},{"key":"2643_CR14","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.1002\/hep.25929","volume":"56","author":"C Cicione","year":"2012","unstructured":"Cicione C, Degirolamo C, Moschetta A (2012) Emerging role of fibroblast growth factors 15\/19 and 21 as metabolic integrators in the liver. Hepatology 56:2404\u20132411","journal-title":"Hepatology"},{"key":"2643_CR15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/cen.13840","volume":"90","author":"RV Clark","year":"2019","unstructured":"Clark RV, Wald JA, Swerdloff RS et al (2019) Large divergence in testosterone concentrations between men and women: frame of reference for elite athletes in sex-specific competition in sports, a narrative review. Clin Endocrinol 90:15\u201322","journal-title":"Clin Endocrinol"},{"key":"2643_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/0895-4356(93)90101-6","author":"G Danan","year":"1993","unstructured":"Danan G, Benichou C (1993) Causality assessment of adverse reactions to drugs-I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol. https:\/\/doi.org\/10.1016\/0895-4356(93)90101-6","journal-title":"J Clin Epidemiol"},{"key":"2643_CR17","first-page":"3","volume":"37","author":"RA Davey","year":"2016","unstructured":"Davey RA, Grossmann M (2016) Androgen receptor structure, function and biology: from bench to bedside. Clin Biochem Rev 37:3\u201315","journal-title":"Clin Biochem Rev"},{"key":"2643_CR18","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1002\/jps.23933","volume":"103","author":"T De Bruyn","year":"2014","unstructured":"De Bruyn T, Sempels W, Snoeys J et al (2014) Confocal imaging with a fluorescent bile acid analogue closely mimicking hepatic taurocholate disposition. J Pharm Sci 103:1872\u20131881. https:\/\/doi.org\/10.1002\/jps.23933","journal-title":"J Pharm Sci"},{"key":"2643_CR19","doi-asserted-by":"publisher","first-page":"939","DOI":"10.5604\/16652681.1222114","volume":"15","author":"FC D\u00edaz","year":"2017","unstructured":"D\u00edaz FC, S\u00e1ez-Gonz\u00e1lez E, Benlloch S et al (2017) Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis. Ann Hepatol 15:939\u2013943. https:\/\/doi.org\/10.5604\/16652681.1222114","journal-title":"Ann Hepatol"},{"key":"2643_CR20","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1111\/liv.12216","volume":"33","author":"Y El Sherrif","year":"2013","unstructured":"El Sherrif Y, Potts JR, Howard MR et al (2013) Hepatotoxicity from anabolic androgenic steroids marketed as dietary supplements: contribution from ATP8B1\/ABCB11 mutations? Liver Int 33:1266\u20131270. https:\/\/doi.org\/10.1111\/liv.12216","journal-title":"Liver Int"},{"key":"2643_CR21","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50394","author":"E Ellis","year":"2003","unstructured":"Ellis E, Axelson M, Abrahamsson A et al (2003) Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor. Hepatology. https:\/\/doi.org\/10.1053\/jhep.2003.50394","journal-title":"Hepatology"},{"key":"2643_CR22","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1515\/hsz-2018-0379","volume":"400","author":"L Fan","year":"2019","unstructured":"Fan L, Joseph JF, Durairaj P et al (2019) Conversion of chenodeoxycholic acid to cholic acid by human CYP8B1. Biol Chem 400:625\u2013628. https:\/\/doi.org\/10.1515\/hsz-2018-0379","journal-title":"Biol Chem"},{"key":"2643_CR23","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1053\/j.gastro.2013.12.032","volume":"146","author":"RJ Fontana","year":"2014","unstructured":"Fontana RJ (2014) Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives. Gastroenterology 146:914\u2013928.e1","journal-title":"Gastroenterology"},{"key":"2643_CR24","doi-asserted-by":"publisher","first-page":"3630","DOI":"10.3390\/ijms19113630","volume":"19","author":"M Garcia","year":"2018","unstructured":"Garcia M, Thirouard L, Sed\u00e8s L et al (2018) Nuclear receptor metabolism of bile acids and xenobiotics: a coordinated detoxification system with impact on health and diseases. Int J Mol Sci 19:3630. https:\/\/doi.org\/10.3390\/ijms19113630","journal-title":"Int J Mol Sci"},{"key":"2643_CR25","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.d028803","author":"JC Garc\u00eda-Ca\u00f1averas","year":"2012","unstructured":"Garc\u00eda-Ca\u00f1averas JC, Donato MT, Castell JV, Lahoz A (2012) Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method. J Lipid Res. https:\/\/doi.org\/10.1194\/jlr.d028803","journal-title":"J Lipid Res"},{"key":"2643_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.07.028","author":"C Garc\u00eda-Monz\u00f3n","year":"2018","unstructured":"Garc\u00eda-Monz\u00f3n C, Petrov PD, Rey E et al (2018) Angiopoietin-like protein 8 is a novel vitamin d receptor target gene involved in nonalcoholic fatty liver pathogenesis. Am J Pathol. https:\/\/doi.org\/10.1016\/j.ajpath.2018.07.028","journal-title":"Am J Pathol"},{"key":"2643_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1747-597X-7-12","volume":"7","author":"N Garevik","year":"2012","unstructured":"Garevik N, Skogastierna C, Rane A, Ekstrom L (2012) Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA reductase. Subst Abuse Treat Prev Policy 7:1\u20136. https:\/\/doi.org\/10.1186\/1747-597X-7-12","journal-title":"Subst Abuse Treat Prev Policy"},{"key":"2643_CR28","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1991.00400100013003","author":"G Glazer","year":"1991","unstructured":"Glazer G (1991) Atherogenic effects of anabolic steroids on serum lipid levels: a literature review. Arch Intern Med. https:\/\/doi.org\/10.1001\/archinte.1991.00400100013003","journal-title":"Arch Intern Med"},{"key":"2643_CR29","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.3134","author":"C Gnewuch","year":"2009","unstructured":"Gnewuch C, Liebisch G, Langmann T et al (2009) Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inflammatory bowel disease. World J Gastroenterol. https:\/\/doi.org\/10.3748\/wjg.15.3134","journal-title":"World J Gastroenterol"},{"key":"2643_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00051-4","author":"B Goodwin","year":"2000","unstructured":"Goodwin B, Jones SA, Price RR et al (2000) A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. https:\/\/doi.org\/10.1016\/S1097-2765(00)00051-4","journal-title":"Mol Cell"},{"key":"2643_CR31","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0246","author":"B Goodwin","year":"2003","unstructured":"Goodwin B, Watson MA, Kim H et al (2003) Differential regulation of rat and human CYP7A1 by the nuclear oxysterol receptor liver X receptor-alpha. Mol Endocrinol. https:\/\/doi.org\/10.1210\/me.2002-0246","journal-title":"Mol Endocrinol"},{"key":"2643_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.08.005","author":"N Grevik","year":"2011","unstructured":"Grevik N, Strahm E, Garle M et al (2011) Long term perturbation of endocrine parameters and cholesterol metabolism after discontinued abuse of anabolic androgenic steroids. J Steroid Biochem Mol Biol. https:\/\/doi.org\/10.1016\/j.jsbmb.2011.08.005","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2643_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.12.014","author":"C Guzm\u00e1n","year":"2013","unstructured":"Guzm\u00e1n C, Benet M, Pisonero-Vaquero S et al (2013) The human liver fatty acid binding protein (FABP1) gene is activated by FOXA1 and PPAR\u03b1; and repressed by C\/EBP\u03b1: implications in FABP1 down-regulation in nonalcoholic fatty liver disease. Biochim Biophys Acta Mol Cell Biol Lipids. https:\/\/doi.org\/10.1016\/j.bbalip.2012.12.014","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"2643_CR34","doi-asserted-by":"publisher","first-page":"513","DOI":"10.2165\/00007256-200434080-00003","volume":"34","author":"F Hartgens","year":"2004","unstructured":"Hartgens F, Kuipers H (2004) Effects of androgenic-anabolic steroids in athletes. Sport Med 34:513\u2013554","journal-title":"Sport Med"},{"key":"2643_CR35","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.s48956","author":"T Kanda","year":"2015","unstructured":"Kanda T, Yokosuka O (2015) The androgen receptor as an emerging target in hepatocellular carcinoma. J Hepatocell Carcinoma. https:\/\/doi.org\/10.2147\/jhc.s48956","journal-title":"J Hepatocell Carcinoma"},{"key":"2643_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00154-5","author":"TA Kerr","year":"2002","unstructured":"Kerr TA, Saeki S, Schneider M et al (2002) Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis. Dev Cell. https:\/\/doi.org\/10.1016\/S1534-5807(02)00154-5","journal-title":"Dev Cell"},{"key":"2643_CR37","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/bjp.2008.165","volume":"154","author":"AT Kicman","year":"2008","unstructured":"Kicman AT (2008) Pharmacology of anabolic steroids. Br J Pharmacol 154:502\u2013521. https:\/\/doi.org\/10.1038\/bjp.2008.165","journal-title":"Br J Pharmacol"},{"key":"2643_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoleng.2010.04.017","author":"DKUN Lee","year":"2003","unstructured":"Lee DKUN, Chang C (2003) Expression and degradation of androgen receptor. J Clin Endocrinol Metab. https:\/\/doi.org\/10.1016\/j.ecoleng.2010.04.017","journal-title":"J Clin Endocrinol Metab"},{"key":"2643_CR39","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3109\/03602532.2012.740048","volume":"45","author":"T Li","year":"2013","unstructured":"Li T, Chiang JYL (2013) Nuclear receptors in bile acid metabolism. Drug Metab Rev 45:145\u2013155","journal-title":"Drug Metab Rev"},{"key":"2643_CR40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178580","author":"Z Li","year":"2017","unstructured":"Li Z, Lin B, Lin G et al (2017) Circulating FGF19 closely correlates with bile acid synthesis and cholestasis in patients with primary biliary cirrhosis. PLoS ONE. https:\/\/doi.org\/10.1371\/journal.pone.0178580","journal-title":"PLoS ONE"},{"key":"2643_CR41","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon.35953","author":"R Liebe","year":"2016","unstructured":"Liebe R, Krawczyk M, Raszeja-Wyszomirska J et al (2016) Heterozygous inactivation of the nuclear receptor PXR\/NR1I2 in a patient with anabolic steroid-induced intrahepatic cholestasis. Hepat Mon. https:\/\/doi.org\/10.5812\/hepatmon.35953","journal-title":"Hepat Mon"},{"key":"2643_CR42","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3389\/fphar.2017.00003","volume":"8","author":"M L\u00f3pez-Riera","year":"2017","unstructured":"L\u00f3pez-Riera M, Conde I, Tolosa L et al (2017) New microRNA biomarkers for drug-induced steatosis and their potential to predict the contribution of drugs to non-alcoholic fatty liver disease. Front Pharmacol 8:3. https:\/\/doi.org\/10.3389\/fphar.2017.00003","journal-title":"Front Pharmacol"},{"key":"2643_CR43","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009098","author":"J Luo","year":"2014","unstructured":"Luo J, Ko B, Elliott M et al (2014) Liver disease: a nontumorigenic variant of FGF19 treats cholestatic liver diseases. Sci Transl Med. https:\/\/doi.org\/10.1126\/scitranslmed.3009098","journal-title":"Sci Transl Med"},{"key":"2643_CR44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193824","author":"L Luo","year":"2018","unstructured":"Luo L, Aubrecht J, Li D et al (2018) Assessment of serum bile acid profiles as biomarkers of liver injury and liver disease in humans. PLoS ONE. https:\/\/doi.org\/10.1371\/journal.pone.0193824","journal-title":"PLoS ONE"},{"key":"2643_CR45","doi-asserted-by":"publisher","first-page":"R165","DOI":"10.1530\/ERC-13-0283","volume":"21","author":"WL Ma","year":"2014","unstructured":"Ma WL, Lai HC, Yeh S et al (2014) Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis. Endocr Relat Cancer 21:R165\u2013R182","journal-title":"Endocr Relat Cancer"},{"key":"2643_CR46","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1998.8431","author":"SC Maness","year":"1998","unstructured":"Maness SC, McDonnell DP, Gaido KW (1998) Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells. Toxicol Appl Pharmacol. https:\/\/doi.org\/10.1006\/taap.1998.8431","journal-title":"Toxicol Appl Pharmacol"},{"key":"2643_CR47","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1208\/s12248-014-9668-6","volume":"17","author":"Q Mao","year":"2015","unstructured":"Mao Q, Unadkat JD (2015) Role of the breast cancer resistance protein (BCRP\/ABCG2) in drug transport\u2014an update. AAPS J 17:65\u201382. https:\/\/doi.org\/10.1208\/s12248-014-9668-6","journal-title":"AAPS J"},{"key":"2643_CR48","doi-asserted-by":"publisher","first-page":"e30014","DOI":"10.1371\/journal.pone.0030014","volume":"7","author":"M Moya","year":"2012","unstructured":"Moya M, Benet M, Guzm\u00e1n C et al (2012) Foxa1 reduces lipid accumulation in human hepatocytes and is down-regulated in nonalcoholic fatty liver. PLoS ONE 7:e30014. https:\/\/doi.org\/10.1371\/journal.pone.0030014","journal-title":"PLoS ONE"},{"key":"2643_CR49","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9163-6","author":"M Okuwaki","year":"2007","unstructured":"Okuwaki M, Takada T, Iwayanagi Y et al (2007) LXR alpha transactivates mouse organic solute transporter alpha and beta via IR-1 elements shared with FXR. Pharm Res. https:\/\/doi.org\/10.1007\/s11095-006-9163-6","journal-title":"Pharm Res"},{"key":"2643_CR50","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1002\/hep.24229","volume":"53","author":"MS Padda","year":"2011","unstructured":"Padda MS, Sanchez M, Akhtar AJ, Boyer JL (2011) Drug induced cholestasis. Hepatology 53:1377\u20131387","journal-title":"Hepatology"},{"key":"2643_CR51","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.24833","author":"WM Pandak","year":"2001","unstructured":"Pandak WM, Bohdan P, Franklund C et al (2001) Expression of sterol 12\u03b1-hydroxylase alters bile acid pool composition in primary rat hepatocytes and in vivo. Gastroenterology. https:\/\/doi.org\/10.1053\/gast.2001.24833","journal-title":"Gastroenterology"},{"key":"2643_CR52","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1080\/17425255.2018.1487399","volume":"14","author":"PD Petrov","year":"2018","unstructured":"Petrov PD, Fern\u00e1ndez-Murga ML, L\u00f3pez-Riera M et al (2018) Predicting drug-induced cholestasis: preclinical models. Expert Opin Drug Metab Toxicol 14:721\u2013738. https:\/\/doi.org\/10.1080\/17425255.2018.1487399","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"9","key":"2643_CR101","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","volume":"29","author":"MW Pfaffl","year":"2001","unstructured":"Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45. https:\/\/doi.org\/10.1093\/nar\/29.9.e45","journal-title":"Nucleic Acids Res"},{"key":"2643_CR53","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/apt.13023","volume":"41","author":"M Robles-Diaz","year":"2015","unstructured":"Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I et al (2015) Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Aliment Pharmacol Ther 41:116\u2013125. https:\/\/doi.org\/10.1111\/apt.13023","journal-title":"Aliment Pharmacol Ther"},{"issue":"6","key":"2643_CR100","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/gkp045","volume":"37","author":"JM Ruijter","year":"2009","unstructured":"Ruijter JM, Ramakers C, Hoogaars WM, Karlen Y, Bakker O, van den Hoff MJ, Moorman AF (2009) Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res 37(6):e45. https:\/\/doi.org\/10.1093\/nar\/gkp045","journal-title":"Nucleic Acids Res"},{"key":"2643_CR54","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22771","author":"FG Schaap","year":"2009","unstructured":"Schaap FG, van der Gaag NA, Gouma DJ, Jansen PLM (2009) High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis. Hepatology. https:\/\/doi.org\/10.1002\/hep.22771","journal-title":"Hepatology"},{"key":"2643_CR55","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1124\/dmd.115.067348","volume":"44","author":"M Schaefer","year":"2016","unstructured":"Schaefer M, Sch\u00e4nzle G, Bischoff D, S\u00fcssmuth RD (2016) Upcyte human hepatocytes: a potent in vitro tool for the prediction of hepatic clearance of metabolically stable compounds. Drug Metab Dispos 44:435\u2013444. https:\/\/doi.org\/10.1124\/dmd.115.067348","journal-title":"Drug Metab Dispos"},{"key":"2643_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2009.09.038","author":"M Scherer","year":"2009","unstructured":"Scherer M, Gnewuch C, Schmitz G, Liebisch G (2009) Rapid quantification of bile acids and their conjugates in serum by liquid chromatography-tandem mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci. https:\/\/doi.org\/10.1016\/j.jchromb.2009.09.038","journal-title":"J Chromatogr B Anal Technol Biomed Life Sci"},{"key":"2643_CR57","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu122","author":"A Sharanek","year":"2014","unstructured":"Sharanek A, Bachour-El Azzi P, Al-Attrache H et al (2014) Different dose-dependent mechanisms are involved in early cyclosporine a-induced cholestatic effects in HepaRG cells. Toxicol Sci. https:\/\/doi.org\/10.1093\/toxsci\/kfu122","journal-title":"Toxicol Sci"},{"key":"2643_CR58","doi-asserted-by":"publisher","first-page":"294278","DOI":"10.1155\/2015\/294278","volume":"2015","author":"M Shen","year":"2015","unstructured":"Shen M, Shi H (2015) Sex hormones and their receptors regulate liver energy homeostasis. Int J Endocrinol 2015:294278. https:\/\/doi.org\/10.1155\/2015\/294278","journal-title":"Int J Endocrinol"},{"key":"2643_CR59","doi-asserted-by":"publisher","first-page":"834","DOI":"10.21037\/tau.2016.07.10","volume":"5","author":"JJ Shoskes","year":"2016","unstructured":"Shoskes JJ, Wilson MK, Spinner ML (2016) Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol 5:834\u2013843","journal-title":"Transl Androl Urol"},{"key":"2643_CR60","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22627","author":"KH Song","year":"2009","unstructured":"Song KH, Li T, Owsley E et al (2009) Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression. Hepatology. https:\/\/doi.org\/10.1002\/hep.22627","journal-title":"Hepatology"},{"key":"2643_CR61","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/hep4.1088","volume":"1","author":"V Sundaram","year":"2017","unstructured":"Sundaram V, Bj\u00f6rnsson ES (2017) Drug-induced cholestasis. Hepatol Commun 1:726\u2013735. https:\/\/doi.org\/10.1002\/hep4.1088","journal-title":"Hepatol Commun"},{"key":"2643_CR62","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2007.04.001","author":"W Tang","year":"2007","unstructured":"Tang W, Norlin M, Wikvall K (2007) Regulation of human CYP27A1 by estrogens and androgens in HepG2 and prostate cells. Arch Biochem Biophys. https:\/\/doi.org\/10.1016\/j.abb.2007.04.001","journal-title":"Arch Biochem Biophys"},{"key":"2643_CR63","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1093\/toxsci\/kfw078","volume":"152","author":"L Tolosa","year":"2016","unstructured":"Tolosa L, G\u00f3mez-Lech\u00f3n MJ, L\u00f3pez S et al (2016) Human Upcyte hepatocytes: characterization of the hepatic phenotype and evaluation for acute and long-term hepatotoxicity routine testing. Toxicol Sci 152:214\u2013229. https:\/\/doi.org\/10.1093\/toxsci\/kfw078","journal-title":"Toxicol Sci"},{"key":"2643_CR64","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2935","author":"TG Travison","year":"2017","unstructured":"Travison TG, Vesper HW, Orwoll E et al (2017) Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the United States and Europe. J Clin Endocrinol Metab. https:\/\/doi.org\/10.1210\/jc.2016-2935","journal-title":"J Clin Endocrinol Metab"},{"key":"2643_CR65","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1111\/j.1872-034X.2008.00381.x","volume":"38","author":"S van der Borght","year":"2008","unstructured":"van der Borght S, van Pelt J, van Malenstein H et al (2008) Up-regulation of breast cancer resistance protein expression in hepatoblastoma following chemotherapy: a study in patients and in vitro. Hepatol Res 38:1112\u20131121. https:\/\/doi.org\/10.1111\/j.1872-034X.2008.00381.x","journal-title":"Hepatol Res"},{"key":"2643_CR66","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1002\/hep.26012","volume":"57","author":"LM van der Velden","year":"2013","unstructured":"van der Velden LM, Golynskiy MV, Bijsmans ITGW et al (2013) Monitoring bile acid transport in single living cells using a genetically encoded F\u00f6rster resonance energy transfer sensor. Hepatology 57:740\u2013752. https:\/\/doi.org\/10.1002\/hep.26012","journal-title":"Hepatology"},{"key":"2643_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.07.022","author":"J Vaquero","year":"2013","unstructured":"Vaquero J, Monte MJ, Dominguez M et al (2013) Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition. Biochem Pharmacol. https:\/\/doi.org\/10.1016\/j.bcp.2013.07.022","journal-title":"Biochem Pharmacol"},{"key":"2643_CR68","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jchromb.2009.11.019","volume":"878","author":"X Xiang","year":"2009","unstructured":"Xiang X, Han Y, Neuvonen M et al (2009) High performance liquid chromatography-tandem mass spectrometry for the determination of bile acid concentrations in human plasma. J Chromatogr B Anal Technol Biomed Life Sci 878:51\u201360. https:\/\/doi.org\/10.1016\/j.jchromb.2009.11.019","journal-title":"J Chromatogr B Anal Technol Biomed Life Sci"},{"key":"2643_CR69","doi-asserted-by":"publisher","DOI":"10.2116\/analsci.25.1155","author":"K Yamaguchi","year":"2010","unstructured":"Yamaguchi K, Murai T, Yabuuchi H et al (2010) Measurement of bile salt export pump transport activities using a fluorescent bile acid derivative. Drug Metab Pharmacokinet. https:\/\/doi.org\/10.2116\/analsci.25.1155","journal-title":"Drug Metab Pharmacokinet"},{"key":"2643_CR70","doi-asserted-by":"publisher","DOI":"10.1002\/jps.23584","author":"K Yang","year":"2013","unstructured":"Yang K, K\u00f6ck K, Sedykh A et al (2013) An updated review on drug-induced cholestasis: mechanisms and investigation of physicochemical properties and pharmacokinetic parameters. J Pharm Sci. https:\/\/doi.org\/10.1002\/jps.23584","journal-title":"J Pharm Sci"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-019-02643-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00204-019-02643-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-019-02643-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:13:49Z","timestamp":1609373629000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00204-019-02643-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":72,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["2643"],"URL":"https:\/\/doi.org\/10.1007\/s00204-019-02643-y","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,1]]},"assertion":[{"value":"27 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}