Ring Finger Protein 6 Mediates Androgen-Induced Granulosa Cell Proliferation and Follicle Growth via Modulation of Androgen Receptor Signaling
Bibliographic record
Abstract
The destiny of the ovarian follicle (growth or atresia) is tightly regulated by the actions and interactions of endocrine, paracrine, and autocrine factors. Although androgens are known to be important in the regulation of folliculogenesis, whether they facilitate or suppress follicular growth has been controversial, and the mechanisms involved are not fully understood. Moreover, the role and regulation of androgen receptor (AR) in mediating androgen signaling during follicular development is not clear. Here, we report that the active androgen dihydrotestosterone upregulates the expression of AR and its E3 ligase ring finger protein 6 (RNF6), increasing site-specific AR polyubiquitination and AR transcriptional activity for soluble Kit ligand (sKit-L) expression in preantral follicle growth. RNF6 silencing suppressed dihydrotestosterone-induced AR ubiquitination (lysine residue 63) and proliferation and suppressed apoptosis in preantral granulosa cells, with these responses being overcome by the presence of exogenous sKit-L. Taken together, our findings support the notion that RNF6 plays an important role in androgen-induced, follicle-stage-dependent follicle growth and that it acts by facilitating AR-mediated granulosa cell sKit-L expression and proliferation. Our findings offer insights into the regulatory mechanism of androgen action in ovarian 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 | 0.000 | 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) | 0.000 | 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".