Regulation of Gonadotropin-Releasing Hormone and Its Receptor Gene Expression by 17β-Estradiol in Cultured Human Granulosa-Luteal Cells*
Bibliographic record
Abstract
There is evidence that GnRH and its binding sites are expressed in numerous extrapituitary tissues, including the primate ovary. However, the factors that regulate ovarian GnRH and its receptor (GnRH-R) remain poorly characterized. Since gonadal steroids are key regulators of ovarian functions, the present study investigated the role of 17beta-estradiol (E2) in regulating GnRH and GnRH-R messenger RNA (mRNA) from human granulosa-luteal cells (hGLCs). RT-PCR was used to isolate the ovarian GnRH-R transcript equivalent to the full-length coding region in the pituitary from hGLCs. Sequence analysis revealed that the ovarian GnRH-R mRNA is identical to its pituitary counterpart. Basal expression studies indicated that GnRH and GnRH-R mRNA levels significantly increased with time in vitro, reaching levels of 160% and 170% on day 8 and 10 of culture, respectively (P < 0.05). Treatment with various concentrations of estradiol (1-100 nM) for 24 h resulted in a dose-dependent decrease (P < 0.05) in GnRH and GnRH-R mRNA levels. Time course studies indicated that short-term treatment (6 h) with E2 (1 nM) had no significant effect on GnRH mRNA levels, while long-term treatment (48 h) with E2 resulted in a 40% decrease (P < 0.001) in GnRH mRNA levels. In contrast, GnRH-R mRNA levels exhibited a biphasic pattern, such that a short-term treatment (6 h) with E2 increased GnRH-R mRNA levels by 20% (P < 0.05), whereas long-term treatment (48 h) resulted in a 60% decrease (P < 0.001) in GnRH-R expression in hGLCs. Cotreatment of estradiol and tamoxifen blocked the E2 induced-regulation of GnRH and its receptor mRNAs, indicating that the E2 effect was mediated through its receptor. In summary, our studies demonstrate that the ovary possesses an intrinsic GnRH axis that is regulated during luteinization in vitro, and that E2 is capable of regulating GnRH and its receptor in the human ovary.
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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) | 0.000 | 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".