Inhibition of estradiol synthesis attenuates renal injury in male streptozotocin-induced diabetic rats

Am J Physiol Renal Physiol. 2011 Sep;301(3):F634-40. doi: 10.1152/ajprenal.00718.2010. Epub 2011 Jun 8.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / prevention & control*
  • Albuminuria / metabolism
  • Albuminuria / prevention & control
  • Anastrozole
  • Animals
  • Aromatase Inhibitors / pharmacology
  • Collagen Type IV / metabolism
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / prevention & control*
  • Disease Models, Animal
  • Estradiol / metabolism*
  • Interleukin-6 / metabolism
  • Male
  • Nitriles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / adverse effects
  • Testosterone / metabolism
  • Transforming Growth Factor beta / metabolism
  • Triazoles / pharmacology

Substances

  • Aromatase Inhibitors
  • Collagen Type IV
  • Interleukin-6
  • Nitriles
  • Transforming Growth Factor beta
  • Triazoles
  • Anastrozole
  • Testosterone
  • Estradiol
  • Streptozocin