Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

Previous reports that investigated the regulation of the NO/soluble guanyly l cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17 beta -estradiol (E2) regulates the alph a (1) and beta (1) subunits of the NO receptor, sGC, at the mRNA and protei n levels in rat uterus. Using real-time quantitative PCR, we found that wit hin 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to dimi nish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC alpha (1) 10% and sGC beta (1) 33% of untreated). This effect was blocked b y the estrogen receptor antagonist, ICI 182,780, indicating that estrogen r eceptor is required. The effect of E2 also was observed in vitro with incub ations of uterine tissue, indicating that the response does not depend on t he secondary release of other hormones or factors from other tissues. Purom ycin did not block the effect, suggesting the effects occur because of pree xisting factors in uterine tissues and do not require new protein synthesis . Using immunoblot analysis, we found that sGC protein levels also were red uced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression.