Sex differences in substrates and clearance products of cortisol and corticosterone synthesis in full-term human umbilical circulation without labor: Substrate depletion matches synthesis in males, but not females
Bibliographic record
Abstract
BACKGROUND: Antenatal impacts on the hypothalamus- pituitary-adrenal axis affect health throughout later life and the impacts on developing males and females often differ. The female fetus at full-term (sampled as scheduled Caesarian section without antecedent labor) both receives more cortisol in umbilical venous blood and adds more cortisol to umbilical arterial circulation than the male. The current study was designed to expand our knowledge of sex-specific, fetal, adrenal steroid synthesis and clearance pathways. METHODS: Paired, full-term, arterial and venous umbilical cord samples were taken at the time of scheduled Caesarian delivery (N = 53, 33 male). Adrenal glucocorticoids (cortisol, corticosterone), cortisol precursor steroids (17-hydroxyprogesterone, 11-deoxycortisol), and cortisol and corticosterone metabolites (cortisone and 11-dehydrocorticosterone), as well as gonadal steroids (testosterone and androstenedione), were quantified by liquid chromatography coupled to tandem mass spectrometry. RESULTS: Both sexes preferentially added corticosterone. Males added more testosterone than females. The female fetus had higher umbilical cord (arterial and venous) concentrations of cortisol, as well as higher total steroid molarity summed across the six adrenal steroids, than males. Depletion of substrate pools of 17-hydroxyprogesterone, 11-deoxycortisol, and cortisone could account for only 20% of net female cortisol synthesis. In contrast, increased fetal synthesis of cortisol was balanced by equivalent molar depletion of substrate pools when the fetus was male. CONCLUSIONS: Preferential fetal corticosterone synthesis in both sexes, and higher concentrations of cortisol in females were confirmed. Differences in adrenal steroidogenesis pathway function in full-term males and females might underlie antenatal programming of hypothalamic-pituitary-adrenal axis function in later life.
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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) | 0.001 | 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".