Transcriptional Regulation of a Disintegrin and Metalloproteinase with Thrombospondin Motif 1 (ADAMTS1) in Bovine Preovulatory Follicles.
Bibliographic record
Abstract
The ovulatory process involves a complex remodeling of the extracellular matrix during which a desintegrin and metalloproteinase with thrombospondin motif 1 (ADAMTS1) is thought to play a key role. However, the transcriptional regulation of ADAMTS1 expression in bovine preovulatory follicles (POF) remains largely unknown. The objectives of the study were to characterize the regulation of ADAMTS1 in bovine follicles prior to ovulation, and to determine its transcriptional control in bovine granulosa cells (GC). Regulation of ADAMTS1 was assessed using total RNAs isolated from bovine POF obtained at various times after human chorionic gonadotropin (hCG) treatment. Results from RT-PCR analyses showed that levels of ADAMTS1 mRNA were very low at 0 h, but significantly increased 6-24 h post-hCG in theca and granulosa cells in vivo. To determine the regulatory mechanisms controlling bovine ADAMTS1 transactivation, primary cultures of GC isolated from bovine dominant follicles of the first wave were used. Foskolin (FSK) stimulation up-regulated ADAMTS1 mRNA expression as observed in vivo. Mutation studies and promoter assays for the bovine ADAMTS1 promoter identified a minimal region conferring full-length basal and FSK-stimulated promoter activities, with both being dependent on Ebox cis-acting elements. Electrophoretic mobility shift assays revealed a key role of upstream stimulating factor (USF) proteins interacting with the Ebox. Binding of USFs with the endogenous ADAMTS1 promoter was confirmed by chromatin immunoprecipitation assays. Increases in ADAMTS1 promoter activity and mRNA levels were observed in GC cultures after FSK and cPKA stimulation, but not after treatment with inhibitors of PKA, ERK1/2 and EGFR. ADAMTS1 promoter binding activity stimulated by FSK and cPKA was inhibited by phosphatase pretreatment. High levels of ADAMTS1 mRNA were also observed after EGF stimulation. Collectively, results from this study unravel some of the molecular control involved in the gonadotropin-dependent regulation of ADAMTS1 in bovine GC prior to ovulation, including cAMP/PKA/EGFR/ERK1/2 signaling pathways and USF protein phosphorylation. This study was supported by NSERC of Canada.
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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 | 0.000 |
| 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".