Retinoic Acid Mediates Transcriptional Repression of Ovine Follicle-Stimulating Hormone Receptor Gene via a Pleiotropic Nuclear Receptor Response Element1
Bibliographic record
Abstract
The FSH receptor (FSHR) and retinoid receptors are critical regulators of gonadal function. Unlike the latter, the FSH receptors are expressed exclusively in ovarian granulosa and testicular Sertoli cells in a developmental fashion. Toward understanding the nature of various transcription factors that direct a tissue- and stage-specific expression of the FSHR gene, we have studied FP4, one of the two footprinting regions (FP3 and FP4) mapped at -241 to -269 and -284 to -303, respectively, upstream of the transcription start site of the ovine FSHR gene. Gel mobility shift assays with FP4 probe revealed two sequence-specific DNA-protein complexes in the presence of nuclear extracts from two immortal gonadal cell lines. Antibody supershift assays demonstrated that retinoic acid receptor (RAR) was involved in the complex 1 whereas steroidogenic factor-1 (SF-1) was present in the complex 2. Mutation studies revealed that DNA binding sites for RAR and SF-1 were overlapping each other within a 19-base pair length of nucleotide sequence of FP4, and a mutation in the half RAR binding site seriously affected SF-1 binding. Reporter assays showed that FP4 conferred SF-1 transactivation as well as RAR-mediated, ligand-dependent repression. Overexpression of SF-1 in a transformed Sertoli cell line partially overcame RAR-mediated suppression. For the first time, our studies reveal a direct retinoid modulation of the gonadotropin receptor promoter and suggest a mechanism by which activators and repressors compete for composite elements providing antagonistic pathways that could modulate the expression of FSHR.
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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 | 0.001 | 0.001 |
| 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".