title: Inhibition of estradiol synthesis attenuates renal injury in male streptozotocin-induced diabetic rats.
abstract: We previously showed that the male streptozotocin (STZ)-induced diabetic rat exhibits decreased circulating testosterone and increased estradiol levels. While supplementation with dihydrotestosterone is partially renoprotective, the aim of the present study was to examine whether inhibition of estradiol synthesis, by blocking the aromatization of testosterone to estradiol using an aromatase inhibitor, can also prevent diabetes-associated renal injury. The study was performed on male Sprague-Dawley nondiabetic, STZ-induced diabetic, and STZ-induced diabetic rats treated with 0.15 mg/kg of anastrozole, an aromatase inhibitor (Da) for 12 wk. Treatment with anastrozole reduced diabetes-associated increases in plasma estradiol by 39% and increased plasma testosterone levels by 187%. Anastrozole treatment also attenuated urine albumin excretion by 42%, glomerulosclerosis by 30%, tubulointerstitial fibrosis by 32%, along with a decrease in the density of renal cortical CD68-positive cells by 50%, and protein expression of transforming growth factor-β by 20%, collagen type IV by 29%, tumor necrosis factor-α by 28%, and interleukin-6 by 25%. Anastrozole also increased podocin protein expression by 18%. We conclude that blocking estradiol synthesis in male STZ-induced diabetic rats is renoprotective.
authors.affiliation: Department of Physiology and Biophysics, Univ. of Mississippi Medical Center, Jackson, 39216, USA.
authors.forename: Michaele B
authors.initials: MB
authors.lastname: Manigrasso
authors.forename: R Taylor
authors.initials: RT
authors.lastname: Sawyer
authors.forename: David C
authors.initials: DC
authors.lastname: Marbury
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Flynn
authors.forename: Christine
authors.initials: C
authors.lastname: Maric
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D000419:Albuminuria / Q000378:metabolism / Q000517:prevention & control; D000077384:Anastrozole; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D024141:Collagen Type IV / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004958:Estradiol / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000009:adverse effects; D013739:Testosterone / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D024141:Collagen Type IV; D015850:Interleukin-6; D009570:Nitriles; D016212:Transforming Growth Factor beta; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone; D004958:Estradiol; D013311:Streptozocin