{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:08:22Z","timestamp":1782234502235,"version":"3.54.5"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UP_1605\/15"],"award-info":[{"award-number":["MC_UP_1605\/15"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["132503"],"award-info":[{"award-number":["132503"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["SRUG2204052159"],"award-info":[{"award-number":["SRUG2204052159"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010414","name":"Health Research Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010414","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Emerging Clinician Scientist","award":["ECSA-2020-001"],"award-info":[{"award-number":["ECSA-2020-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Excess production of adrenal-derived 11-oxygenated androgens is observed in congenital adrenal hyperplasia, premature adrenarche, and polycystic ovary syndrome. 11-Ketotestosterone is equipotent to testosterone but does not decline with age. To date, the precise hepatic metabolism of 11-oxygenated androgens and subsequent urinary metabolite excretion have not been characterised.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>We employed an integrated approach combining an in vivo oral androgen challenge with an ex vivo normothermic machine liver perfusion (NMLP) model to characterise human hepatic 11-oxygenated androgen metabolism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Women with polycystic ovary syndrome were randomised to receive 150\u2005mg of either oral dehydroepiandrosterone or 11-ketoandrostenedione (11KA4) for 7 days (n = 10 for each), with collection of 24-hour urine samples for multi-steroid profiling by liquid chromatography-tandem mass spectrometry pre- and post-intervention. We employed human liver tissue explants (n = 3) alongside a whole human liver NMLP model (n = 3) to characterise ex vivo 11-oxygenated androgen metabolism.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In ex vivo studies, the main metabolites identified were 11\u03b2-hydroxyandrosterone and 11\u03b2-hydroxyetiocholanolone. In vivo priming of the 11-oxygenated pathway with oral 11KA4 resulted in significant increases of urinary 11\u03b2-hydroxyandrosterone, 11\u03b2-hydroxyetiocholanolone, and 11-ketoetiocholanolone, all known to overlap with glucocorticoid metabolism. In addition, we observed significant increases in the urinary excretion of 11-ketoandrosterone (11KAn).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Using in vivo and ex vivo approaches, we report the predominance of 11\u03b2-hydroxy metabolites, highlighting the pivotal role of hepatic 11\u03b2-hydroxysteroid dehydrogenase type 1 (HSD11B1) activity in 11-oxygenated androgen metabolism. We identify 11KAn as the only metabolite without overlap with glucocorticoid metabolism, underscoring its specificity and biomarker potential. NMLP represents a novel integrated model to study human hepatic steroid metabolism.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf166","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T21:44:58Z","timestamp":1755035098000},"page":"340-347","source":"Crossref","is-referenced-by-count":3,"title":["Hepatic metabolism of 11-oxygenated androgens in humans: an integrated <i>in vivo<\/i> and <i>ex vivo<\/i> approach"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6887-8333","authenticated-orcid":false,"given":"Tara","family":"McDonnell","sequence":"first","affiliation":[{"name":"Androgens in Health and Disease Research Group, Academic Division of Endocrinology, Department of Medicine, Royal College of Surgeons in Ireland , Dublin D09 V2N0 ,","place":["Ireland"]},{"name":"Department of Endocrinology, Beaumont Hospital , Dublin D09 V2N0 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amarah V","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham , Birmingham B15 2TT ,","place":["United Kingdom"]},{"name":"Medical Research Council Laboratory of Medical Sciences, London W12 0HS ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Clarke","sequence":"additional","affiliation":[{"name":"Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, Institute of Biomedical Research, University of Birmingham , Birmingham B15 2TT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Schiffer","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham , Birmingham B15 2TT ,","place":["United Kingdom"]},{"name":"Medical Research Council Laboratory of Medical Sciences, London W12 0HS ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela E","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Systems Science, School of Medical Sciences, College of Medicine and Health, University of Birmingham , Birmingham B15 2TT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Cussen","sequence":"additional","affiliation":[{"name":"Androgens in Health and Disease Research Group, Academic Division of Endocrinology, Department of Medicine, Royal College of Surgeons in Ireland , Dublin D09 V2N0 ,","place":["Ireland"]},{"name":"Department of Endocrinology, Beaumont Hospital , Dublin D09 V2N0 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyu","family":"Fan","sequence":"additional","affiliation":[{"name":"Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, Institute of Biomedical Research, University of Birmingham , Birmingham B15 2TT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus","family":"Hann","sequence":"additional","affiliation":[{"name":"Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, Institute of Biomedical Research, University of Birmingham , Birmingham B15 2TT ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Mao","sequence":"additional","affiliation":[{"name":"Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, Institute of Biomedical Research, University of Birmingham , Birmingham B15 2TT 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Department of Medicine, Royal College of Surgeons in Ireland , Dublin D09 V2N0 ,","place":["Ireland"]},{"name":"Department of Surgery, RCSI University of Medicine and Health Sciences , Dublin D02 YN77 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benson","family":"Jacob","sequence":"additional","affiliation":[{"name":"Androgens in Health and Disease Research Group, Academic Division of Endocrinology, Department of Medicine, Royal College of Surgeons in Ireland , Dublin D09 V2N0 ,","place":["Ireland"]},{"name":"Department of Endocrinology, Beaumont Hospital , Dublin D09 V2N0 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sherlock","sequence":"additional","affiliation":[{"name":"Androgens in Health and Disease Research Group, Academic Division of Endocrinology, Department of Medicine, Royal College of Surgeons in Ireland , Dublin D09 V2N0 ,","place":["Ireland"]},{"name":"Department of 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