High Neonatal Leptin Exposure Enhances Brain GR Expression and Feedback Efficacy on the Adrenocortical Axis of Developing Rats
Bibliographic record
Abstract
Leptin modifies the activity of the hypothalamic-pituitary-adrenal axis in adult rodents and inhibits the production of glucocorticoids from human and rat adrenals in vitro. During development, high levels of circulating leptin and low levels of corticosterone secretion are observed together with adrenal hyporesponsiveness to stress. As chronic neonatal leptin administration reduced stress-induced corticotropin-releasing factor mRNA expression and ACTH secretion in pups, we determined whether elevated leptin levels enhanced the feedback effect of glucocorticoids on the hypothalamic-pituitary-adrenal axis. In naive pups we found a highly significant inverse relationship between plasma levels of leptin and corticosterone (P < 0.01) during postnatal d 6-20. We tested the ability of dexamethasone (1 or 10 microg/kg BW, ip, -3 h before stress) to suppress ether-induced ACTH secretion in 10-d-old pups that were treated during the neonatal period (d 2-9) with either vehicle or leptin (1 or 3 mg/kg BW, ip, daily). The expressions of brain GR and MR in vehicle- or leptin-treated neonates were determined by in situ hybridization and Western blotting. Chronic leptin treatment enhanced the ability of dexamethasone to suppress ACTH secretion after stress, and the low dose of dexamethasone was discriminant. Leptin treatment increased GR mRNA levels in the hypothalamic paraventricular nucleus (P < 0.05) and in the dentate gyrus of the hippocampus in a dose-dependent fashion. Hippocampal GR protein concentrations were increased by leptin treatment (P < 0.05). Expression of MR mRNA was not modified. Thus, the ability of leptin to enhance glucocorticoid feedback in pups is mediated in part by changes in brain GR. The high circulating leptin concentrations found in developing pups might be critical to regulate glucocorticoid production, GR levels, and stress responses. As leptin levels in pups vary with maternal diet, leptin might represent an important mediator of the maternal environment on 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".