Sex hormones differentially modulate STAT3-dependent antioxidant responses during oxidative stress in renal proximal tubule cells.
OBJECTIVE
Gender-associated dimorphism in renal oxidative stress may be related to the protective effects of estrogens or the adverse effects of testosterone. Signal transducer and activator of transcription-3 (STAT3)-dependent transcription is vital in renal antioxidant responses, which may be differentially regulated by sex hormones.


METHODS
Renal proximal tubule cells were treated with 400 μM H2O2 in the presence or absence of 100 nM dihydrotestosterone (DHT), 100 nM 17β-estradiol (E2) or dominant-negative STAT3 (dnSTAT3). Production of reactive oxygen species (ROS), phosphorylation/transcriptional activation of STAT3 and promoter activity of the STAT3-regulated antioxidant gene (MnSOD) were determined.


RESULTS
After treatment with H2O2, DHT decreased tyrosine phosphorylation/transcriptional activity of STAT3 and promoter activity of MnSOD while E2 increased them. Consequently, DHT augmented while E2 attenuated ROS production. Effects of dnSTAT3 were similar to DHT.


CONCLUSIONS
Sex hormones may influence renal oxidative stress through differential regulation of STAT3-dependent antioxidant responses.
Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, U.S.A.
Dustin K
DK
Reed
Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, U.S.A. iarany@umc.edu.
Istvan
I
Arany
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013552:Swine
D000975:Antioxidants; D012739:Gonadal Steroid Hormones; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D013196:Dihydrotestosterone; D004958:Estradiol; D013482:Superoxide Dismutase
MnSOD; STAT3; androgen; estrogen; oxidative stress; renal