ESTRADIOL ENHANCES THIAZIDE-SENSITIVE NACL COTRANSPORTER DENSITY IN THE APICAL PLASMA-MEMBRANE OF THE DISTAL CONVOLUTED TUBULE IN OVARIECTOMIZED RATS

Recent data suggest that sex hormones affect the thiazidesensitive NaC l cotransporter (TSC) density or binding capacity (Chen, Z., D.A. Vaug hn, and D.D. Fanestil, 1994. J. Am. Soc. Nephrol, 5:1112-1119). Thus, we determined the effect of ovariectomy (OVX) and estrogen replacement on the ultrastructural localization of TSC in rat kidney using immuno cytochemistry. Kidneys of intact female (CON) and OVX rats fed ad libi tum for 6 and 9 wk or pair-fed for 9 wk were processed for transmissio n electron microscopy. Immunogold localization of rat TSC (rTSC1) demo nstrated intense label in the apical plasma membrane of CON distal con voluted tubule (DCT). In OVX DCT, rTSC1 label and apical plasma membra ne microprojections were decreased. Western blots of renal membrane pr otein from pair-fed CON and OVX revealed bands at 129-135 kD, but the OVX signal was reduced. Morphometric analyses demonstrated that inject ing 10 mu g/ kg body weight 17 beta-estradiol subcutaneously 4x/wk in OVX rats restored DCT apical microprojections and label density for rT SC1. Thus, in OVX rats (a) rTSC1 immunoreactive renal membrane protein is reduced; (b) apical plasma membrane complexity and immunogold labe l for rTSC1 in DCT is decreased; and (c) estradiol replacement restore s DCT ultrastructure and rTSC1 label to normal. We conclude that estro gen enhances the density of rTSC1 in the DCT, and may alter renal Na t ransport by this mechanism.