Regulation of Cyclin D2 Expression and Degradation by Follicle-Stimulating Hormone During Rat Granulosa Cell Proliferation In Vitro1
Bibliographic record
Abstract
Cyclin D2 (CCND2, encoded by Ccnd2) plays an important role in the induction of early-to-mid G1 phase transition and is required for granulosa cell proliferation during ovarian folliculogenesis. In the present study, we investigated the role of follicle-stimulating hormone (FSH) in the regulation of cyclin D2 expression and degradation during rat granulosa cell proliferation in vitro. FSH acutely increased granulosa cell Ccnd2 mRNA abundance and CCND2 protein content as well as proliferation. FSH-induced granulosa cell CCND2 protein content and proliferation were mimicked by forskolin and attenuated by inhibitors of protein kinase A (PKA; H89) and phosphatidylinositol 3-kinase (PI3K; LY294002) as well as PKA catalytic subunit (PRKACA) small interfering RNA (siRNA) and dominant-negative Akt (dn-Akt) but were not affected by mitogen-activated protein kinase kinase 1/2 (MEK1/2; U0126). Interestingly, FSH also enhanced CCND2 protein degradation in granulosa cells, a process involving a PKA-mediated ubiquitin-proteasome degradation pathway. Taken together, these results demonstrate that FSH acutely regulated CCND2 expression through both PKA and PI3K signaling pathways during granulosa cell proliferation and also accelerated its ubiquitination-proteasomal degradation, which may prevent overstimulation of granulosa cell proliferation and follicular growth.
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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".