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Testosterone lowers microvascular ET‐B receptor responsiveness in women with PCOS
Author(s) -
Wenner Megan M,
Taylor Hugh S,
Stachenfeld Nina S
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb559
Subject(s) - medicine , endocrinology , polycystic ovary , testosterone (patch) , vasodilation , antagonist , microdialysis , antagonism , saline , area under the curve , receptor , insulin resistance , obesity , central nervous system
High testosterone (T) exposure is a characteristic of polycystic ovary syndrome (PCOS). T is also associated with greater ET‐1 plasma concentration, which may contribute to vascular dysfunction in women with PCOS. To test the hypothesis that T‐related impaired microvascular function associated with PCOS is mediated by ET‐B receptors, we suppressed endogenous sex hormones in 4 Control (23±2 years, 35.2±1.3kg/m 2 ) and 4 women with PCOS (22±1 years, 36.2±2.5kg/m 2 ) using a GnRH antagonist (GnRHa, 9 days); we then administered T (2.5 mg/day, oral) the last 4 days of GnRHa. We measured cutaneous vascular conductance (CVC) responses to local heating with laser Doppler flowmetry during microdialysis infusions of saline, ET‐A (BQ‐123), and ET‐B (BQ‐788) receptor antagonists. Baseline CVC was similar during GnRHa in Control (0.096±0.061 AU/mmHg) and PCOS (0.102±0.010 AU/mmHg). T administration tended to increase baseline CVC in Control (0.213±0.106 AU/mmHg; P =0.09) but not PCOS (0.082±0.018 AU/mmHg). Heat‐induced vasodilation during saline was similar between Control and PCOS. However, T administration attenuated heat‐induced vasodilation during ET‐B antagonism in Control (Δ GnRHa 1.13±0.14, T 0.43±0.12 AU/mmHg; P <0.01) but not PCOS (Δ GnRHa 1.38±0.32, T 1.06±0.34 AU/mmHg). ET‐A antagonism had minimal effect in either group. Women with PCOS show blunted ET‐B receptor sensitivity during T exposure. HL093450