REGULATION OF LUTEAL FUNCTION

妊娠的建立和维持需要协调 黄体功能的激素调节。广泛调查 来自外部的实验室已经确立了雌二醇和催乳素在 这样的规定。我们的研究使我们分离出黄体基因， 20α-羟基类固醇脱氢酶(20α-HSD)，其表达为 显著抑制PRL的活性。我们还发现了一种新的蛋白质，名为 PRAP，它与短形式的 PRL受体，其表达受雌二醇的严格调控。 最有趣的是，PRL对20pha-HSD基因表达的抑制 通过PRL受体的短形式发生。在…的第一部分 本次研究，我们将确定PRL-信号转导的机制 通过PRL受体短型使用黄体来源的细胞系 在我们实验室里产生的。我们还将确定PRP在PRL中的角色 通过这种受体类型发出信号。因为对黄体的刺激 20α-HSD在降低黄体生成素/前列腺素F/2a的表达中起关键作用 孕酮的产生和分娩，我们将调查 这些激素上调20α-HSD的分子机制 基因表达。我们最近的调查显示， 黄体细胞中催乳素和雌二醇的协同作用涉及催乳素 刺激雌激素受体(α和β)mRNAs和 雌二醇诱导PRAP的表达。雌二醇和催乳素也起作用 共同作用于延伸因子2，一种与蛋白质有关的多肽 翻译，以分别提高其水平和状态 磷酸化。因此，我们将对最后一个具体目标进行调查 雌二醇和催乳素在黄体中的分子机制 细胞中参与蛋白磷酸化的表达和状态 它们各自的信号和蛋白质翻译。

The establishment and maintenance of pregnancy requires the coordinate hormonal regulation of corpus luteum function. Extensive investigation from out laboratory has established a key role for estradiol and PRL in such regulation. Our research has led us to isolate a corpus luteum gene, 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), whose expression is markedly inhibited by PRL. We have also discovered a novel protein, named PRAP, that associates with the intracellular domain of the short form of the PRL-receptor and whose expression is tightly regulated by estradiol. Most interestingly, the PRL inhibition of the 20alpha-HSD gene expression occurs through the short form of the PRL-receptor. In the first part of this investigation, we will determine the mechanism of PRL-signaling through the PRL-receptor short form using luteal derived cell lines generated in our laboratory. We will also define the role of PRAP in PRL signaling through this receptor type. Because stimulation of luteal 20alpha-HSD expression by LH/PGF/2a plays a key role in lowering progesterone production and allowing for parturition, we will investigate the molecular mechanism by which these hormones up regulate 20alpha-HSD gene expression. Our recent investigations have revealed that the synergism between PRL and estradiol action in luteal cells involves PRL stimulation of both estradiol receptor (alpha and beta) mRNAs and estradiol induction of PRAP expression. Estradiol and PRL also act together on elongation factor 2, a peptide involved in protein translation, to respective enhance its levels and state of phosphorylation. We will therefore investigate in the last specific aim the molecular mechanism by which estradiol and PRL attest in the luteal cell, the expression and state of phosphorylation of proteins involved in their respective signaling and in protein translation.