P75117β-Oestradiol activates oestrogen receptors in a sex-specific manner in rat cardiac fibroblasts leading to sex dimorphic collagen I and III expression
Bibliographic record
Abstract
Purpose: Female pressure-overloaded hearts show less collagen I and III gene expression and cardiac fibrosis, compared to males. This suggests an inhibitory effect of 17β-Oestradiol (E2) on collagens. Since E2 mediates its effect mainly via activation of its receptors, oestrogen receptor (ER) alpha (α) and beta (β), we analysed here the ER-mediated effects on collagen I and III expression in isolated rat cardiac fibroblasts from both sexes. Methods: Cardiac fibroblasts were isolated from adult female and male Wistar rats. Cellular localization of ER in cardiac fibroblasts was detected by immunofluorescence staining and expression of both ER was determined by western blot, with and without E2 (10-8M). Isolated cells were treated with E2, vehicle, ERα- and ERβ-agonist (10-7M) and/or pre-treated with ICI 182,780 (10-5M) for 24h, followed by expression analysis of collagen I and III by qRT-PCR and western blot. Results: E2-treatment led to a nuclear translocation of both ER in cardiac fibroblasts, suggesting their functional activity as transcription factors. In cells from female rat hearts, E2 led to a significant down-regulation of collagen I and III gene and protein expression. In contrast, there was a significant increase of both collagens in male cardiac fibroblasts by E2. E2-effects could be inhibited by ICI 182, 780 indicating the involvement of ER. Further analysis using specific ER-agonists revealed that ERα-agonist-treatment led to a significant down-regulation of collagen I and III mRNA in female cardiac fibroblasts. ERβ-agonist had no effects. By contrast, ERβ-agonist-treatment of male cardiac fibroblasts increased mRNA levels of both collagens, but no changes with the ERα-agonist were detected. Further studies to identify sex differences in ER protein levels showed similar levels of ERα between sexes, but higher expression of ERβ in female cells compared to males. After E2-treatment, ERα protein was significantly up-regulated only in male cardiac fibroblasts, whereas ERβ was not changed in both sexes. In addition, E2-induced activation of ERα by phosphorylating Ser118 could only be shown in female cardiac fibroblasts. Conclusion: Sex-specific regulation of collagen I and III expression by E2 in cardiac fibroblasts might be responsible for sex differences in cardiac fibrosis. This might be due to sex dimorphic ER expression and regulation. Understanding how E2/ER mediate sex differences in cardiac remodeling may help to design sex-specific pharmacological interventions.
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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 | 0.006 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.000 | 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".