Hepatic metabolism of 11-oxygenated androgens in humans: an integrated in vivo and ex vivo approach
Authors' conclusion
Using 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.
Study context
- Population
- Women with PCOS (in vivo); human liver tissue explants and whole human livers in normothermic machine liver perfusion (NMLP) (ex vivo)human liver tissue explants 3 · whole human livers in NMLP 3
- Participants
- 10 vs 10
- Comparison
- Oral DHEA vs oral 11-ketoandrostenedione, 150 mg for 7 days
- Oral dehydroepiandrosteronen = 10
- 11KA4n = 10
- Outcome
- Hepatic 11-oxygenated androgen metabolism
Methodological detailsrandomised oral androgen challenge, ex vivo normothermic machine liver perfusion (NMLP), human liver tissue explants, 24-hour urine multi-steroid profiling by liquid chromatography-tandem mass spectrometry pre- and post-intervention
- Randomised oral androgen challenge
- Ex vivo normothermic machine liver perfusion (NMLP)
- Human liver tissue explants
- 24-hour urine multi-steroid profiling by liquid chromatography-tandem mass spectrometry pre- and post-intervention
Main finding
As reported in the abstract
- Ex vivo: main metabolites were 11β-hydroxyandrosterone and 11β-hydroxyetiocholanolone
- In vivo oral 11KA4: significant increases in urinary 11β-hydroxyandrosterone, 11β-hydroxyetiocholanolone and 11-ketoetiocholanolone, all overlapping with glucocorticoid metabolism
- Significant increases in urinary 11-ketoandrosterone (11KAn) excretion
Original publication
Hepatic metabolism of 11-oxygenated androgens in humans: an integrated in vivo and ex vivo approach. Eur J Endocrinol. Published 8 August 2025. doi:10.
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