Differential Role of Progesterone Receptor Isoforms in the Transcriptional Regulation of Human Gonadotropin-Releasing Hormone I (GnRH I) Receptor, GnRH I, and GnRH II
Bibliographic record
Abstract
Hypothalamic GnRH is a decapeptide that plays a pivotal role in mammalian reproduction by stimulating the synthesis and secretion of gonadotropins via binding to the GnRH receptor on the pituitary gonadotropins. It is hypothesized that sex steroids may regulate GnRH I (a classical form of GnRH), GnRH II (a second form of GnRH), and GnRH I receptor (GnRHRI) at the transcriptional level in target tissues. Thus, in the present study a role for progesterone (P4) in the regulation of GnRH I, GnRH II, and GnRHRI was investigated using a human neuronal medulloblastoma cell line (TE671) as an in vitro model. The cells were transfected with human GnRHRI promoter-luciferase constructs, and promoter activities were analyzed after P4 treatment by luciferase and beta-galactosidase assay. The mRNA levels of GnRH I and GnRH II were analyzed by RT-PCR. Treatment of TE671 cells with P4 resulted in a decrease in GnRHRI promoter activity compared with the control level in a dose- and time-dependent manner. Cotreatment of these cells with RU486, an antagonist of P4, reversed P4-induced inhibition of GnRHRI promoter activity, suggesting that the P4 effect is mediated by P4 receptor (PR). In the cells transfected with a full-length of PR A- or PR B-expressing vector, overexpression of PR A increased the sensitivity toward P4 in an inhibition of GnRHRI promoter, whereas PR B increased transcriptional activity of GnRHRI promoter in the presence of P4. However, PR B itself did not act as a transcriptional activator of GnRHRI promoter. Because TE671 cells have been recently demonstrated to express and synthesize two forms of GnRHs, we also investigated the regulation of GnRH mRNAs by P4. In the present study, P4 increased GnRH I mRNA levels in a time- and dose-dependent manner. This stimulatory effect of P4 in the regulation of GnRH I mRNAs was significantly attenuated by RU486, whereas no significant difference in the expression level of GnRH II was observed with P4 or RU496. Interestingly, although the expression level of PR B was low compared with that of PR A, P4 action on the GnRH I gene was mediated by PR B. In conclusion, these results indicate that P4 is a potent regulator of GnRHRI at the transcriptional level as well as GnRH I mRNA. This distinct effect of P4 on the GnRH system may be derived from different pathways through PR A or PR B.
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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) | 0.000 | 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) | 0.001 | 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 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".