Progesterone-dependent decidualization of the human endometrium is mediated by cAMP
Progesterone-dependent decidualization of the human endometrium is mediated by cAMP
复制标题
DOI：
10.1007/bf02820507
复制
发表时间：
1997-06-01
期刊：
影响因子：
3.7
通讯作者：
Handwerger, S
中科院分区：
文献类型：
--
作者：
Brar, AK;Frank, GR;Handwerger, S
孕激素是调节子宫内膜细胞蜕膜化的关键因素，但参与介导孕激素作用的信号转导途径尚不清楚。体外研究表明，cAMP激动剂可以在不存在性类固醇的情况下刺激蜕膜化，这表明cAMP途径在蜕膜化中的作用。在这篇文章中，我们已经使用了一个体外培养模型的炔雌醇依赖的人子宫内膜间质细胞的蜕膜化检查炔雌醇诱导的蜕膜化是否与激活cAMP信号转导通路，其中催乳素基因的表达是一个标志物的蜕膜化。经过约3天的滞后期，孕酮诱导催乳素分泌和细胞内cAMP水平升高。到第15天，cAMP和催乳素水平分别约为第3天的10倍和60倍。cAMP水平的变化与催乳素分泌呈正相关。前列腺素E-2（PGE（2））可增强孕酮依赖的蜕膜化，与第3天相比，第15天催乳素分泌和cAMP水平也增加约2 - 4倍，而PGE（2）单独使用不诱导蜕膜化，不刺激催乳素分泌或细胞内cAMP积累。相反，全反式视黄酸，减弱孕酮依赖的蜕膜化，显着（p < 0.05）降低催乳素分泌和cAMP水平。此外，蛋白激酶A（PKA）抑制剂，8-溴腺苷-3 '，5'-环硫代磷酸，显着（p < 0.05）抑制孕酮依赖性催乳素的表达。由于PGE（2）受体亚型EP 2的激活可刺激腺苷酸环化酶，因此对子宫内膜细胞进行了逆转录-聚合酶链反应（RT-PCR）分析。与未处理的对照组相比，单独用孕酮和雌二醇处理或用PGE处理的细胞中EP 2 mRNA的表达被诱导（2）。数据表明，cAMP信号转导级联在孕酮依赖的蜕膜化过程中被激活。
Progesterone is a key factor in regulating endometrial cell decidualization, but the signal transduction pathways involved in mediating the effects of progesterone are not known. A role of the cAMP pathway in decidualization has been suggested by in vitro studies demonstrating that cAMP agonists can stimulate decidualization, in the absence of sex steroids. In this article, we have used an in vitro culture model of progesterone-dependent decidualization of human endometrial stromal cells to examine whether progesterone-induced decidualization is associated with activation of the cAMP signal transduction pathway in which the prolactin gene expression is a marker of decidualization. Following a lag period of approx 3 d, progesterone induced prolactin secretion and elevated intracellular cAMP levels. By d 15, cAMP and prolactin levels were approx 10- and 60-fold greater, respectively, than those on d 3. Changes in cAMP levels showed a positive correlation with prolactin secretion. Prostaglandin E-2 (PGE(2)),which enhances progesterone-dependent decidualization, also increased both prolactin secretion and cAMP levels approx two-to fourfold on d 15 compared with d 3, whereas PGE(2) alone, which does not induce decidualization, did not stimulate prolactin secretion or intracellular cAMP accumulation. Conversely, all-trans retinoic acid, which attenuates progesterone-dependent decidualization, significantly (p < 0.05) decreased both prolactin secretion and cAMP levels. Furthermore, the protein kinase A (PKA) inhibitor, 8-bromoadenosine-3',5'-cyclic monophosphorothioate, significantly (p < 0.05) suppressed progesterone-dependent prolactin expression. Since activation of the PGE(2) receptor subtype EP2 stimulates adenylate cyclase, reverse transcription-polymerase chain reaction (RT-PCR) analysis of endometrial cells was undertaken. Expression of EP2 mRNA was induced in cells treated with progesterone and estradiol alone or with PGE(2), compared with untreated controls, The data suggest that the cAMP signal transduction cascade is activated during progesterone-dependent decidualization.