GPER mediates the effects of 17β-estradiol in cardiac mitochondrial biogenesis and function

Considering the sexual dimorphism described in cardiac mitochondrial function and oxidative stress, we aimed to investigate the role of 17 beta-estradiol (E-2) in these sex differences and the contribution of E-2 receptors to these effects. As a model of chronic deprivation of ovarian hormones, we used ovariectomized (OVX) rats, half of which were treated with E-2. Ovariectomy decreased markers of cardiac mitochondrial biogenesis and function and also increased oxidative stress, whereas E-2 counteracted these effects. In H9c2 cardiomyocytes we observed that G-protein coupled estrogen receptor (GPER) agonist mimicked the effects of E-2 in enhancing mitochondrial function and biogenesis, whereas GPER inhibitor neutralized them. These data suggest that E-2 enhances mitochondrial function and decreases oxidative stress in cardiac muscle, thus it could be responsible for the sexual dimorphism observed in mitochondrial biogenesis and function in this tissue. These effects seem to be mediated through GPER stimulation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.