Role of prostaglandins in the suppression of apoptosis in hen granulosa cells by transforming growth factor alpha
Bibliographic record
Abstract
Although transforming growth factor alpha (TGF-alpha) is known to be an important survival factor for granulosa cells, the cellular and molecular mechanisms involved are uncertain. The purpose of the present study was to investigate the possible involvement of prostaglandins in the anti-apoptotic action of TGF-alpha. Hen granulosa cells from healthy prehierarchical follicles (2-6 mm) cultured in serum-free medium underwent spontaneous apoptosis as demonstrated by DNA fragmentation and nuclear chromatin condensation. TGF-alpha (20 ng ml(-1)) stimulated maximum synthesis of prostaglandins (PGE and PGF) in granulosa cells and completely inhibited serum deprivation-induced apoptosis. The addition of an inhibitor of cyclooxygenase (COX; N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS398) or ibuprofen) or phospholipase A(2) (PLA(2); aristolochic acid, 2-p-amylcinnamoyl amino-4-chlorobenzoic acid (ONO-RS-82) or arachidonyl triflouro methyl ketone (TFMK)), to the culture medium markedly suppressed the TGF-alpha-induced prostaglandin synthesis and significantly increased granulosa cell apoptosis. The apoptotic effect of NS398 and aristolochic acid was completely inhibited by exogenous prostaglandins (PGF(2 alpha), PGE(1), PGE(2)) and arachidonic acid, respectively. However, exogenous prostaglandins failed to inhibit the PLA(2) inhibitor-induced apoptotic DNA fragmentation, implying that in addition to prostaglandins, arachidonic acid or leukotrienes may be important in transducing the anti-apoptotic action of TGF-alpha. In the absence of exogenous TGF-alpha, prostaglandins had no significant influence on granulosa cell apoptosis induced by serum withdrawal. These findings indicate that prostaglandin synthesis is a necessary, but not sufficient, event in the suppression of granulosa cell apoptosis by TGF-alpha. Whether arachidonic acid or leukotrienes are important in the anti-apoptotic action of TGF-alpha in hen granulosa cells remains to be determined.
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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".