Differential Regulation of Two Forms of Gonadotropin-Releasing Hormone Messenger Ribonucleic Acid in Human Granulosa-Luteal Cells**This work was supported by grants from the Medical Research Council of Canada.
Bibliographic record
Abstract
Until recently, the primate brain was thought to contain only one form of GnRH known as mammalian GnRH (GnRH-I). The recent cloning of a second form of GnRH (GnRH-II) with characteristics of chicken GnRH-II in the primate brain has prompted a reevaluation of the role of GnRH in reproductive functions. In the present study, we investigated the hormonal regulation of GnRH-II messenger RNA (mRNA) and its functional role in the human granulosa-luteal cells (hGLCs), and we provided novel evidence for differential hormonal regulation of GnRH-II vs. GnRH-I mRNA expression. Human GLCs were treated with various concentrations of GnRH-II, GnRH-II agonist (GnRH-II-a), or GnRH-I agonist (GnRH-I-a; leuprolide) in the absence or presence of FSH or human CG (hCG). The expression levels of GnRH-II, GnRH-I, and GnRH receptor (GnRHR) mRNA were investigated using semiquantitative or competitive RT-PCR. A significant decrease in GnRH-II and GnRHR mRNA levels was observed in cells treated with GnRH-II or GnRH-II-a. In contrast, GnRH-I-a revealed a biphasic effect (up- and down-regulation) of GnRH-I and GnRHR mRNA, suggesting that GnRH-I and GnRH-II may differentially regulate GnRHR and their ligands (GnRH-I and GnRH-II). Treatment with FSH or hCG increased GnRH-II mRNA levels but decreased GnRH-I mRNA levels, further indicating that GnRH-I and GnRH-II mRNA levels are differentially regulated. To investigate the physiological role of GnRH-II, hGLCs were treated with GnRH-II or GnRH-II-a in the presence or absence of hCG, for 24 h, and progesterone secretion was measured by RIA. Both GnRH-II and GnRH-II-a inhibited basal and hCG-stimulated progesterone secretion, effects which were similar to the effects of GnRH-I treatment on ovarian steroidogenesis. Next, hGLCs were treated with various concentrations of GnRH-II, GnRH-II-a, or GnRH-I-a; and the expression levels of FSH receptor and LH receptor were investigated using semiquantitative RT-PCR. A significant down-regulation of FSH receptor and LH receptor was observed in cells treated with GnRH-II, GnRH-II-a, and GnRH-I-a, demonstrating that GnRH-II and GnRH-I may exert their antigonadotropic effect by down-regulating gonadotropin receptors. Interestingly, GnRH-II and GnRH-II-a did not affect basal and hCG-stimulated intracellular cAMP accumulation, suggesting that the antigonadotropic effect of GnRH-II may be independent of modulation of cAMP levels. Taken together, these results suggest that GnRH-II may have biological effects similar to those of GnRH-I but is under differential hormonal regulation in the human ovary.
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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".