Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20α-hydroxysteroid dehydrogenase
Regulation of progesterone levels during pregnancy and parturition by signal transducer and activator of transcription 5 and 20α-hydroxysteroid dehydrogenase
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DOI：
10.1210/me.2004-0302
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发表时间：
2005-02-01
影响因子：
--
通讯作者：
Weinstein, Y
中科院分区：
文献类型：
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作者：
Piekorz, RP;Gingras, B;Weinstein, Y
两种高度相关的信号转导和转录激活因子Stat5a和Stat5b是乳腺和卵巢中催乳素信号传导的主要介质。Stat5b或Stat5a和Stat5b缺乏症可导致妊娠中期流产，并与卵巢20 α -羟基类固醇脱氢酶（20 α - hsd）升高和血清黄体酮下降相关，而黄体酮通常仅在分娩前立即下降。为了确定20 α - hsd在妊娠和分娩期间对孕酮代谢和Stat5功能的相对贡献，我们通过基因破坏建立了20 α - hsd缺陷小鼠品系。缺乏20α - hsd的小鼠维持高孕酮水平，并表现出分娩延迟数天，这表明20α - hsd以必要和非冗余的方式调节前列腺素F-2alpha受体下游的分娩。此外，20 α - hsd缺乏部分纠正了与Stat5b缺乏相关的妊娠流产，支持催乳素激活Stat5b在抑制20 α - hsd基因表达方面的重要作用，从而维持维持妊娠所需的黄体酮水平。
The two highly related signal transducers and activators of transcription (Stats), Stat5a and Stat5b, are major mediators of prolactin signaling in both the mammary gland and in the ovary. Deficiencies in Stat5b, or in both Stat5a and Stat5b, result in loss of pregnancy during midgestation and are correlated with an increase in ovarian 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD) and a decrease in serum progesterone, which normally declines only immediately before parturition. To determine the relative contribution of 20alpha-HSD to progesterone metabolism and Stat5 function during pregnancy and parturition, we created a 20alpha-HSD-deficient strain of mice by gene disruption. Mice deficient for 20alpha-HSD sustain high progesterone levels and display a delay in parturition of several days demonstrating that 20alpha-HSD regulates parturition downstream of the prostaglandin F-2alpha receptor in an essential and nonredundant manner. Moreover, 20alpha-HSD deficiency partially corrected the abortion of pregnancies associated with Stat5b deficiency, supporting the concept that prolactin activation of Stat5b is important in suppressing 20alpha-HSD gene expression and thereby allowing the maintenance of progesterone levels that are required to sustain pregnancy.