(VP106) TESTOSTERONE INDUCES CARDIAC REMODELLING AND CARDIAC DYSFUNCTION, AND ALTERS FATTY ACID METABOLISM IN A RODENT MODEL OF POLYCYSTIC OVARY SYNDROME

Background: The incidence of cardiovascular disease (CVD) is increased in the endocrine-metabolic condition of polycystic ovary syndrome (PCOS) which impacts 10-15% of females across the lifespan. The mechanisms of cardiac dysfunction in PCOS related to hyperandrogenemia, and androgen receptor (AR) and estrogen receptor (ER) activation and energy substrate utilization remain unclear. 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 AND RESULTS: An established rodent model of PCOS and the metabolic syndrome, and controls were treated with testosterone (T) at age 6 weeks (adolescence) for 12 weeks. Cardiac function was assessed using transthoracic doppler echocardiography. Lipid metabolism, Lipogenic, AR, ER and other metabolic gene and protein expression was performed using RTPCR and SDSPAGE western blot.

Results: PCOS-prone animals exhibited left ventricular (LV) hypertrophy, with increased LV mass to body weight ratio (551.6 ± 38.85 mg vs 999 ± 96.17 mg, p< 0.05) and beta-myosin heavy chain protein compared to controls. 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 elevated B-type natriuretic peptide in PCOS-prone compared to controls. T treatment increased LV mass, IVCT and IVRT in controls but did not exacerbate cardiac re-modelling in PCOS-prone animals. T treatment increased cardiac Peroxisome proliferator-activation receptor-⍺, Acyl-CoA carboxylase, and reduced ER-⍺ and AR protein expression in both T treated control and PCOS-prone animals.

Conclusion: Testosterone adversely impacts cardiac re-modelling and function in control conditions, and alters fatty acid metabolism, and AR and ER activation in control and PCOS-prone conditions. These mechanistic findings may help to explain increased CVD in hyperandrogenemic conditions of PCOS and provide insight into the potential role of estrogen and anti-androgen therapies in mitigating cardiovascular risk.