Source:Molecular and Cellular Endocrinology
Author(s): Seema Bansal, Kanwaljit Chopra
Postmenopausal diabetic women represent a specific risk group with a greater incidence of vascular deficits as compared with age-matched men or non-diabetic women. 17β-estradiol is the mainstay therapy for menopause and associated complications; however, its vasculoprotective effect is lost in women with diabetes. Although, exact mechanism of dichotomous effect of estrogen has not been delineated but it may be due to, differential activation of ER-α and β during disease conditions such as diabetes. Thus main objective of our study was to characterize the specific estrogen receptor which could be selectively targeted to achieve vasculoprotection in postmenopausal diabetic situation. A significant impairment in glycemic and lipid profile, decreased ACh-induced endothelium dependent relaxation, impaired endothelial integrity, and rise in inflammatory and oxidative stress markers were observed in ovariectomized type 2 diabetic rats as compared to sham rats. These markers were further correlated with aortic eNOS levels. Treatment with selective ER-α receptor agonist markedly while 17β-estradiol partially ameliorated these alterations along with enhanced aortic eNOS levels. However, ER-β agonist did not show any effect. Our data suggests that selective ER-α activation could be an important pharmacological target, to mimic the beneficial effect of estradiol in cardiovascular disorders, especially in postmenopausal diabetic state.
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