Abstract 5681: GPR30 is Required for the Pro-apoptotic Effects of Estrogen in Vascular Smooth Muscle Cells
Bibliographic record
Abstract
Rapid and non-genomic effects of estradiol (EST) may be mediated through the G-Protein-coupled receptor dubbed GPR30 receptor. The present studies tested the hypothesis that GPR30 expression, which we demonstrate is readily detectable in freshly isolated vascular tissue but is decreasingly detectable in cultured VSMCs, mediates the effects of EST to alter ERK phosphorylation status and apoptosis. In freshly isolated aortic tissue, EST-stimulated ERK phosphorylation whereas in cultured VSMCs, EST inhibits ERK phosphorylation in a dose-dependent manner. However, gene transfer of GPR30 resulted in EST-mediated stimulation of ERK phosphorylation (138±4%, n=10), which is in contrast to the effects of EST in GFP-expressing primary culture of VSMCs (68±3%, n=14). EST-mediated stimulation of ERK subsequent to heterologous GPR30 expression was pertussis toxin-sensitive and PI3 kinase-dependent; under these conditions, EST also inhibited PKA activation. In contrast, in the absence of GPR30 expression in cultured VSMC, EST stimulated PKA activity and inhibited ERK phosphorylation. We also assessed the impact of GPR30 expression on EST-mediated regulation of VSMCs apoptosis. In cultured VSMC transduced with GFP vector (control conditions), EST (10 nM) mediated a decrease in VSMC apoptosis (80±2%, n=7), an effect that was marginally but significantly enhanced by gene transfer of ER α (71±3%, n=7). The anti-apoptotic effect of EST was attenuated by co-incubation with the PKA inhibitor Rp-cAMP. However, PI3 kinase inhibition did not affect estradiol’s anti-apoptotic actions. In contrast, gene transfer of GPR30 into the VSMC resulted in enhancement of apoptotic rates following EST treatment (169±2%, n=7), and this GPR30-mediated pro-apoptotic effect of EST was attenuated by the PI3 kinase inhibitor, but not by Rp-cAMP. Thus, the effect of EST on vascular smooth muscle cell apoptosis is likely dependent on the balance between ER-mediated PKA activation and GPR30-mediated PKA inhibition and PI3 kinase activation. Taken together, we postulate that modulation of GPR30 expression and/or activity may be an important determinant of the effects of estradiol in the vasculature.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.004 |
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".