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

• Published in: Molecular and cellular endocrinology 2016-01, Vol.420, p.116-124
• Main Authors: Sbert-Roig, Miquel, Bauzá-Thorbrügge, Marco, Galmés-Pascual, Bel M., Capllonch-Amer, Gabriela, García-Palmer, Francisco J., Lladó, Isabel, Proenza, Ana M., Gianotti, Magdalena
• Format: Article
• Language: English
• Subjects: 17β-estradiol; Animals; Biomarkers - metabolism; Body Weight - drug effects; Cardiac muscle; Cell Line; Estradiol - blood; Estradiol - pharmacology; Female; GPER; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondrial biogenesis; Myocardium - metabolism; Myocytes, Cardiac - metabolism; Organ Size - drug effects; Organelle Biogenesis; Ovariectomy; Oxidative stress; Oxidative Stress - drug effects; Progesterone - blood; Rats, Wistar; Receptors, Estrogen - metabolism; Receptors, G-Protein-Coupled - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2015.11.027

Considering the sexual dimorphism described in cardiac mitochondrial function and oxidative stress, we aimed to investigate the role of 17β-estradiol (E2) in these sex differences and the contribution of E2 receptors to these effects. As a model of chronic deprivation of ovarian hormones, we used ovariectomized (OVX) rats, half of which were treated with E2. Ovariectomy decreased markers of cardiac mitochondrial biogenesis and function and also increased oxidative stress, whereas E2 counteracted these effects. In H9c2 cardiomyocytes we observed that G-protein coupled estrogen receptor (GPER) agonist mimicked the effects of E2 in enhancing mitochondrial function and biogenesis, whereas GPER inhibitor neutralized them. These data suggest that E2 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. •Estradiol enhances mitochondrial function in cardiac muscle.•Estradiol also reduces cardiac oxidative stress.•The effects of estradiol on mitochondrial function are modulated by GPER.