Distinct role of estrogen receptor-alpha and beta on postmenopausal diabetes-induced vascular dysfunction

作者：Bansal Seema; Chopra Kanwaljit^*

来源：General and Comparative Endocrinology, 2014, 206: 51-59.

DOI：10.1016/j.ygcen.2014.06.013

• Menopause
• Diabetes
• Vascular dysfunction
• Estrogen receptor

Estrogen is known to influence vascular functions and insulin sensitivity, but the relative contribution of estrogen receptor (ER) isoforms in postmenopausal diabetes-induced vascular dysfunction is unclear. The aim of the present study was to delineate the distinct role of estrogen receptor-alpha and beta beta on the vascular function in ovariectomized diabetic rats. Age matched 60 female sprague dawley rats (200-250 g) were divided in nine groups. Bilateral ovariectomy was performed and streptozotocin was used to induce experimental diabetes. Rats were administered with 10 mu g/kg; s.c. of a nonselective estrogen receptor agonist, 17-beta estradiol (E2), selective ER-a agonist (4,4%26apos;,4 %26apos;%26apos;-(4-propyl-[1H] pyrazole-1,3,5-triyl) tris phenol (PPT) and selective ER-beta agonist, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) for 4 weeks after STZ injection. Treatment with selective ER-alpha agonist and E2 improved the impaired glycemic and lipid profile in ovariectomized diabetic rats, however selective ER-beta agonist did not show any effect. Vascular endothelial dysfunction was assessed by acetylcholine and sodium nitroprusside-induced endothelium dependent and independent relaxation in isolated rat aortic ring preparation as well as by electron microscopy of thoracic aorta. Further, serum thiobarbituric acid reactive substances, tumour necrotic factor-alpha and interleukin-1 beta and C-reactive protein were estimated to assess oxidative stress and vascular inflammation. Treatment with ER-alpha agonist markedly and E2 partially improved vascular function and endothelial integrity along with reduction in serum TBARS and inflammatory cytokines. However, ER-beta agonist did not show any improvement in vascular functions, oxidative stress or inflammation. These findings suggest that selective targeting of ER-alpha receptors results in vasculoprotection in the state of hypoestrogenicity and diabetes.

• 出版日期2014-9-15