Gonadotropin-releasing hormone regulates transcription of the inhibin B co-receptor, TGFBR3L, via early growth response one
Bibliographic record
Abstract
Follicle-stimulating hormone (FSH), a product of pituitary gonadotrope cells, regulates gonadal function and fertility. FSH production is stimulated by gonadotropin-releasing hormone (GnRH) and activin-class ligands of the TGFβ family. Inhibin A and B are TGFβ proteins that suppress FSH synthesis by competitively binding activin type II receptors in concert with the co-receptors betaglycan (TGFBR3) and TGFBR3L. Betaglycan mediates the actions of both inhibins and is broadly expressed. In contrast, TGFBR3L is inhibin B-specific and selectively expressed in gonadotropes. This cell-restricted expression is driven, in part, by steroidogenic factor 1 (SF-1, NR5A1), which stimulates Tgfbr3l/TGFBR3L transcription via two conserved promoter elements. Tgfbr3l expression is lost in mice lacking SF-1 in gonadotropes. However, SF-1 alone is unlikely to fully explain gonadotrope-restricted Tgfbr3l/TGFBR3L expression. Here, we report that GnRH induces binding of the transcription factor, early growth response 1 (EGR1), to the murine Tgfbr3l and human TGFBR3L promoters at a conserved cis-element between the two SF-1 binding sites. In homologous LβT2 cells, GnRH stimulation of Tgfbr3l/TGFBR3L promoter-reporters depends on EGR1 binding to this cis-element. In heterologous cells, over-expressed EGR1 independently and synergistically with SF-1 activates Tgfbr3l/TGFBR3L promoter-reporter activities. In vivo, Tgfbr3l mRNA expression is reduced in the pituitaries of: 1) GnRH-deficient mice, 2) wild-type mice treated with a GnRH receptor antagonist, and 3) gonadotrope-specific Egr1 knockout mice. Gonadectomy, which increases GnRH pulse frequency, enhances Tgfbr3l expression in control but not gonadotrope-specific Egr1 knockouts. Collectively, these data indicate that GnRH stimulates Tgfbr3l/TGFBR3L transcription via EGR1, which acts with SF-1 through conserved promoter elements.
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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) | 0.003 | 0.002 |
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".