Anti-Hypertrophic Effect of Estradiol in Cardiomyocytes is Mediated by GPER1

Previous data have shown that E2 prevents cardiomyocyte hypertrophy induced by endothelin-1 (ET-1) and Angiotensin II, acting through the increase of atrial and type-B natriuretic peptides (ANP and BNP) levels. In recent years, a membrane-bound E2 receptor has emerged, G protein-coupled estrogen receptor 1 (GPER1), which mediates many estrogenic effects. In this work, we investigated whether E2 protective signaling effect on ET1-induced hypertrophy is mediated via GPER1 receptor. Newborn rat cardiomyocytes were isolated and cultured in DMEM supplemented with 10% fetal bovine serum with antibiotic and antimycotic. Cells were treated for 48h with ET-1 (10 nM) in the presence or not of E2 (10 nM). In some experiments GPER1 antagonist (G15, 10 nM) was added to the medium. ET-1 induced an increase in cardiac myocyte area compared to control group. Treatment with E2 partially inhibited the hypertrophic effect of ET-1. Treatment with G15 reversed antihypertrophic effect of E2. Moreover, ET-1 upregulated ANP and ...