Androgen and Estrogen Receptor Activation Impacts Cardiac Function in a PCOS-Prone Rodent Model
Bibliographic record
Abstract
Abstract Introduction: The global risk and incidence of cardiovascular disease (CVD) is increased in polycystic ovary syndrome (PCOS). Early risk factors and subclinical CVD includes atherogenic dyslipidemia, obesity, insulin resistance, blood pressure, atherosclerosis and impaired cardiac function. Androgen exposure is associated with onset of adiposity, impaired insulin-glucose and lipid metabolism, and cardiac dysfunction. The mechanisms of increased risk of CVD and cardiac dysfunction in PCOS related to hyperandrogenemia, AR and estrogen receptor (ER) activation remain unclear. Aim: The aim of this study was to investigate the effect of androgen treatment on cardiac AR and ER activation, fatty acid metabolism and cardiac function in a PCOS-prone rodent model. Methods: A PCOS-prone rodent model at 6 wks of age with obesity, apoB-remnant lipemia and insulin resistance, and controls were treated with testosterone for 12 weeks. Cardiac function was assessed using transthoracic doppler echocardiography (M-Mode 2D-imaging), lipogenic, AR, ER and other metabolic gene and protein expression were assessed using RTPCR and SDS-PAGE western blot. Results: PCOS-prone animals exhibited left ventricular (LV) hypertrophy, with increased LV mass to body weight (551.6 ± 38.85 mg vs 999 ± 96.17 mg, p<0.05), LV posterior wall diastolic diameter and LV internal diastolic diameter compared to controls. Isovolumetric relaxation time (IVRT) was prolonged (15.91 ± 1.591 msec vs 23.75 ± 0.722 msec, p<0.05). Mild systolic dysfunction was evidenced by increased isovolumetric contraction time (IVCT; 22.5 ± 1.348 msec vs 28.96 ± 1.248 msec, p<0.05) and decreased % ejection fraction and % fractional shortening in PCOS-prone compared to controls. T treatment increased LV mass, IVCT and IVRT in controls but did not exacerbate cardiac function in PCOS-prone animals. T treatment increased cardiac protein expression of PPAR-⍺ in PCOS-prone and controls, and T increased ACC in controls. AR protein expression tended to be reduced, and ER-⍺ was reduced in both T treated control and PCOS-prone animals. Conclusions: The PCOS-prone rodent model demonstrates early cardiac LV hypertrophy and diastolic-systolic dysfunction and T treatment alters fatty acid metabolism, and AR and ER activation are associated with altered cardiac morphology and function in the PCOS-prone and control conditions.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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".