ETA subtype receptor sensitivity to testosterone contributes to microvascular dysfunction in PCOS

Abstract

Hyperandrogenism and endothelial dysfunction are hallmarks of Polycystic Ovary Syndrome (PCOS). We hypothesized that testosterone (T)‐related inhibition of endothelium‐mediated vasodilation in women with PCOS occurs via the ETA receptor. For 11 days we suppressed sex hormones with a gonadotropin releasing hormone antagonist (GnRHa) in women with (PCOS, n=6, 23.2±0.7 y, 35.4±1.7 kg/m2) and without (C, n=7, 22.0±1.6 y, 34.1±1.1 kg/m2) PCOS; we added testosterone (T, 2.5 mg/day) for days 8–11. On days 4 and 11, we measured cutaneous vascular conductance (CVC) with laser Doppler flowmetry during local heating and microdialysis infusions of an ETA (BQ‐123) or ETB (BQ‐788) receptor antagonist. Compared to GnRHa, during T ETA block enhanced heat‐induced vasodilation in PCOS (ΔCVC 1.74±0.23, Δ2.15±0.18 for GnRHa, T P< 0.05), with no T effect in C. In both groups, ETB block blunted heat‐induced vasodilation, but less so with T than GnRHa (PCOS: ΔCVC 1.29 ±0.32, 0.84±0.27; C: ΔCVC 0.95±0.21, 0.51±0.13, GnRHa, T P< 0.05). The increased CVC with ETA blockade indicates removal of vasoconstrictor tone and suggests T contributes to constriction via an ETA receptor mechanism in PCOS. HL093450