title: Distinct role of estrogen receptor-alpha and beta on postmenopausal diabetes-induced vascular dysfunction.
abstract: 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-α and beta β on the vascular function in ovariectomized diabetic rats. Age matched 60 female sprague dawley rats (200-250g) were divided in nine groups. Bilateral ovariectomy was performed and streptozotocin was used to induce experimental diabetes. Rats were administered with 10μg/kg; s.c. of a nonselective estrogen receptor agonist, 17-β estradiol (E2), selective ER-α agonist (4,4',4″-(4-propyl-[1H] pyrazole-1,3,5-triyl) tris phenol (PPT) and selective ER-β agonist, 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) for 4weeks after STZ injection. Treatment with selective ER-α agonist and E2 improved the impaired glycemic and lipid profile in ovariectomized diabetic rats, however selective ER-β 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-α agonist markedly and E2 partially improved vascular function and endothelial integrity along with reduction in serum TBARS and inflammatory cytokines. However, ER-β agonist did not show any improvement in vascular functions, oxidative stress or inflammation. These findings suggest that selective targeting of ER-α receptors results in vasculoprotection in the state of hypoestrogenicity and diabetes.
authors: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors: Seema
authors: S
authors: Bansal
authors: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. Electronic address: dr_chopra_k@yahoo.com.
authors: Kanwaljit
authors: K
authors: Chopra
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D038321:Glycemic Index; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress; D017698:Postmenopause; D051381:Rats; D017207:Rats, Sprague-Dawley; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011422:Propionates
chemical_list: D016207:Cytokines; D004958:Estradiol; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D009570:Nitriles; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C506487:ESR1 protein, human
keywords: Diabetes; Estrogen receptor; Menopause; Vascular dysfunction