Effects of Sex Hormones on Na ⁺/Glucose Cotransporter of Renal Proximal Tubular Cells following Oxidant Injury

Abstract

It was reported that reactive oxygen metabolites play an important role in the pathogenesis of several renal diseases including glomerulonephritis, ischemia and acute tubular necrosis. However, the effect of oxidants and protective effect of sex steroid hormones on Na⁺/glucose cotransporter of renal proximal tubular cells is not yet elucidated. In the present study, we examined the effect of sex steroid hormones against tert-butyl hydroperoxide (t-BHP)-induced alteration of Na⁺/glucose cotransporter activity in primary cultured rabbit renal proximal tubule cells (PTCs). t-BHP inhibited α-methyl- D-glucopyranoside (α-MG) uptake in a dose-dependent manner. t-BHP-induced inhibition of α-MG uptake was due not to K_m but to the decrease of V_max. 0.5 m M t-BHP-induced inhibition of α-MG uptake was significantly blocked by estradiol-17β, but not by progesterone and testosterone. This protective effect was not blocked by estrogen receptor antagonist or transcription and translation inhibitor. In addition, 0.5 m M t-BHP increased [³H]-arachidonic acid (AA) release and Ca²⁺ uptake. These effects of t-BHP were also significantly blocked by estradiol-17β, but not by progesterone and testosterone. Protective efficacy of estradiol-17β on t-BHP-induced inhibition of α-MG uptake is exhibited between antioxidants and iron chelators. In conclusion, estradiol-17β, but not progesterone and testosterone, partially prevented t-BHP-induced inhibition of α-MG uptake through its antioxidant activity dependent upon phenol structures and inhibition of AA release and Ca²⁺ influx.