Trial reportEuropean journal of endocrinology2025
Hepatic metabolism of 11-oxygenated androgens in humans: an integrated in vivo and ex vivo approach.
Trial report in European journal of endocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Toward reliable preoperative prediction of urinary stone composition: critical considerations for imaging and clinical data integration.Urolithiasis · 2025Article
- Comprehensive characterization of 21-hydroxylase deficiency in a Chinese pediatric cohort: phenotype, steroid profiles and genetics.Frontiers in endocrinology · 2025Article
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Authors and funding
18 authors.
Funding
Abstract
objectiveExcess 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.
designWe 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.
methodsWomen with polycystic ovary syndrome were randomised to receive 150 mg 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.
resultsIn ex vivo studies, the main metabolites identified were 11β-hydroxyandrosterone and 11β-hydroxyetiocholanolone. In vivo priming of the 11-oxygenated pathway with oral 11KA4 resulted in significant increases of urinary 11β-hydroxyandrosterone, 11β-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).
conclusionsUsing in vivo and ex vivo approaches, we report the predominance of 11β-hydroxy metabolites, highlighting the pivotal role of hepatic 11β-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.
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