{Reference Type}: Journal Article
{Title}: Cardioprotection of 17β-estradiol against hypoxia/reoxygenation in cardiomyocytes is partly through up-regulation of CRH receptor type 2.
{Author}: Cong B;Xu Y;Sheng H;Zhu X;Wang L;Zhao W;Tang Z;Lu J;Ni X;
{Journal}: Mol Cell Endocrinol
{Volume}: 382
{Issue}: 1
{Year}: Jan 2014 25
{Factor}: 4.369
{DOI}: 10.1016/j.mce.2013.09.002
{Abstract}: Estrogens have been suggested to exert cardioprotection through maintaining endogenous cardioprotective mechanisms. In the present study, we investigated whether estrogens protect cardiomyocytes against hypoxia/reoxygenation (H/R) via modulating urocortins (UCNs) and their receptor corticotrophin-releasing hormone receptor type 2 (CRHR2). We found that 17β-estradiol (E2) enhanced UCN cardioprotection against H/R and increased CRHR2 expression in neonatal rat cardiomyocytes. E2 protected cardiomyocytes against H/R, which was impaired by CRHR2 antagonist or knockdown of CRHR2. Estrogen receptor α (ERα) antagonist treatment or ERα knockdown could abolish E2-induced CRHR2 up-regulation. Moreover, knockdown of Sp1 also attenuated E2-induced CRHR2 up-regulation. Ovariectomy resulted in down-regulation of CRHR2 and Sp-1 in myocardium of mice, which was restored by E2 or ERα agonist treatment. These results suggest that estrogens act on ERα to up-regulate CRHR2 expression in cardiomyocytes, thereby enhancing cardioprotection of UCNs against H/R.