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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus
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Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

机译：雌二醇快速抑制大鼠子宫中可溶性鸟苷酸环化酶的表达

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摘要

Previous reports that investigated the regulation of the NO/ soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic com- pounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demon- strate that 17β-estradiol (E2) regulates the α1 and β1 subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC αl 10/100 and sGC β1 33/100 of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis. we found that sGC protein levels also were reduced 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.
机译：以前研究雌激素化合物对NO /可溶性鸟苷酸环化酶（sGC）/ cGMP途径的调节的报道主要集中于各种组织中NO，NO产生酶和cGMP的水平。在这项研究中，我们证明17β-雌二醇（E2）在大鼠子宫的mRNA和蛋白水平上调节NO受体sGC的α1和β1亚基。使用实时定量PCR，我们发现在体内对大鼠施用E2 1小时内，sGC mRNA水平开始下降。 3小时后，sGC mRNA表达最大减低（未处理的sGCα1/ 100和sGCβ133/100）。该作用被雌激素受体拮抗剂ICI 182,780阻断，表明需要雌激素受体。在子宫组织的温育中也观察到了E2的作用，表明该反应不依赖于其他激素或其他组织因子的二次释放。嘌呤霉素没有阻断这种作用，表明这种作用是由于子宫组织中预先存在的因素而发生的，不需要新的蛋白质合成。使用免疫印迹分析。我们发现E2在与sGC mRNA类似的时间过程中也降低了sGC蛋白水平。我们得出结论，在大鼠子宫中雌激素水平升高（由于sGC表达降低）下，sGC在NO / sGC / cGMP调节途径中起着至关重要的作用。

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