Actions and Interactions of Thyroid Hormone and Follicle-Stimulating Hormone in the Regulation of Rat Granulosa Cell Apoptosis.
Bibliographic record
Abstract
Thyroid hormone (T3) is important for normal reproduction function and dysregulation of TH support is associated with reproductive disorders, including impaired follicular development. Our preliminary studies indicate that FSH increases preantral follicle growth in vitro, a response markedly enhanced by T3. However, the nature of this hormonal interaction is poorly understood. This study is aimed to improve our understanding on the cellular and molecular mechanisms by which T3 regulates ovarian follicle growth, and specifically on the expression and actions of intracellular survival and death intermediates in the regulation of granulosa cell fate and follicle destiny. In the present study, we investigated the possible involvement of the Src and phosphatidylinositol 3-kinase (PI3-K)/Akt survival pathway in the regulation of granulosa cell fate. We have demonstrated by Western blot analysis that, while ineffective alone, T3 markedly enhanced FSH (100 ng/ml)-induced phospho-Src and phospho-Akt contents in granulosa cells in vitro. Although the expression of the anti-apoptotic protein Xiap and the pro-apoptotic ligand (FasL) were also not altered by T3 alone (10-10 to 10-7 M), the presence of T3 significantly increased Xiap content and down-regulated FasL expression induced by FSH. The effects of T3 were concentration-dependent, with maximal responses observable at 10-9 M. Interestingly, FSH and T3 together decreased granulosa cell Fas expression, although neither of the hormone alone elicited a significant response. In addition, addition of the cell death intermediate ceramide to granulosa cell cultures significantly induced apoptosis (as determined by TUNEL) which was attenuated by either FSH or T3. The present of both hormones did not elicit a greater protective effect than either hormone alone. Taken together, the findings of the present study demonstrate that thyroid hormone potentiates the cell survival action of FSH through up-regulation of Xiap and down-regulation of Fas and FasL which is associated with the activation of the Src&PI3K/Akt pathway (supported in part by grants from the National Natural Science Foundation of China and the Canadian Institutes of Health Research). (poster)
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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) | 0.001 | 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 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".