Hypothalamic progesterone receptor-A mediates gonadotropin surges, self priming and receptivity in estrogen-primed female mice
Bibliographic record
Abstract
Ovarian progesterone (Prog) is an essential steroid hormone for the secretion of GnRH and reproductive behavior. It exerts primary effects through the progesterone receptor (PR). When analyzed separately in vitro, PR isoforms (PR-A, PR-B) display striking differences in transcriptional activity. The present study was undertaken to determine the in vivo impact of each isoform on hypothalamic function in female mice with ablation of a single isoform, either PR-A or PR-B. To this end, we used single-cell RNA analyses, reverse transcriptase real-time (q)PCR mRNA analyses of punched-out tissue, immunohistochemistry, and reproductive behavior. We provide evidence for the requirement of PR-A in individual ventrolateral ventromedial nucleus (vlVMN) neurons for Prog-facilitated proceptive and receptive behaviors in estrogen benzoate (EB)-primed females and the reciprocal male interactions. We clarify histological and molecular mechanisms of PR isoform activity by showing that (1) PR-A is predominant in individual vlVMN neurons controlling female lordosis circuitry, whilst (2) PR-B is predominant in those VMN subdivisions that provide for amplification of PR-A activity. We go on to demonstrate that PR-A is dominant in the anteroventral periventricular nucleus but not the arcuate nucleus that feed fibers into and around the VMN. In the medial preoptic area, high levels of GnRH RNA in EB-primed PR-A-expressing mice were seen coincident with increased plasma LH levels. Two consecutive GnRH pulses enhanced LH only in primed PR-A-expressing females. In all, the findings are consistent with the hypothesis that hypothalamic PR-A-mediated genomic activities result in reproductive behavior coordinated with ovulation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".