title: Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury.
abstract: Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol.
authors.affiliation: Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Soljancic
authors.forename: Arnaldo Lopez
authors.initials: AL
authors.lastname: Ruiz
authors.forename: Kiran
authors.initials: K
authors.lastname: Chandrashekar
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Maranon
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
authors.forename: Jane F
authors.initials: JF
authors.lastname: Reckelhoff
authors.forename: Luis A
authors.initials: LA
authors.lastname: Juncos
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology / Q000517:prevention & control*; D000077384:Anastrozole; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000652:urine; D003404:Creatinine / Q000097:blood; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009919:Orchiectomy; D011507:Proteinuria / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013739:Testosterone / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000077384:Anastrozole; D047072:Aromatase Inhibitors; D015815:Cell Adhesion Molecules; D003404:Creatinine; D009570:Nitriles; D013739:Testosterone; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C110936:Havcr1 protein, rat
keywords: androgens; kidney injury molecule-1; sex; vascular endothelial growth factor
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