Hepatic metabolism of 11-oxygenated androgens in humans: an integrated <i>in vivo</i> and <i>ex vivo</i> approach
Bibliographic record
Abstract
OBJECTIVE: 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. DESIGN: 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. METHODS: Women 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. RESULTS: In 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). CONCLUSIONS: 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".