Sex hormones differentially modulate STAT3-dependent antioxidant responses during oxidative stress in renal proximal tubule cells.

Abstract 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. 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. 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. Sex hormones may influence renal oxidative stress through differential regulation of STAT3-dependent antioxidant responses.