Inhibition of Steroidogenic Response to Adrenocorticotropin by Leptin: Implications for the Adrenal Response to Maternal Separation in Neonatal Rats
Bibliographic record
Abstract
Previous studies have shown that leptin can regulate the adrenocortical axis. Neonatal rodents exhibit a period of adrenal hyporesponsiveness to stress in the first 2 wk of life, and we determined the role of leptin as a mediator of this process. We examined the direct effects of leptin on neonatal adrenal steroidogenic responses to ACTH under basal conditions and after 24-h maternal separation. In isolated adrenocortical cells from as early as postnatal d 5 (PND5) and throughout the neonatal period, acute (2.5 h) incubation with leptin significantly inhibited ACTH-stimulated corticosterone and aldosterone secretion without affecting cAMP production. In PND10 pups, 24-h maternal separation and the resulting rapid decline in plasma leptin levels increased basal corticosterone and aldosterone secretion in vivo and in isolated cells, but did not modify the ability of leptin to inhibit stimulated steroid production in vitro. Maternal separation in PND10 pups increased adrenal expression of steroidogenic acute regulatory protein (StAR) and peripheral-type benzodiazepine receptor (PBR) proteins as well as all steroidogenic enzymes measured (3beta-hydroxysteroid dehydrogenase, P450C11B1, and P450C11B2). Leptin (1 mg/kg body weight, i.p.) replacement during maternal separation did not affect basal corticosterone output, but reduced corticosterone secretion and StAR and PBR protein expression induced by exogenous ACTH challenge (20 or 80 microg/kg body weight, i.p.). These results indicate that leptin inhibits ACTH-stimulated secretion of corticosterone and aldosterone, at least through a rapid reduction in the expression of StAR and PBR protein in the neonatal adrenal gland. As leptin concentrations in pups are controlled to a large extent by the maternal diet, these results emphasize the key role of leptin to mediate the maternal influence on the adrenocortical axis of the infant.
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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 | 0.001 |
| 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".