CELLULAR SIGNALS IN OVULATION AND LUTEINIZATION

促黄体生成素(黄体生成素)激增启动两个独特的过程 脊椎动物卵巢-排卵和黄体化。两者都需要表达式 和激活特定的核受体。孕激素受体 和SF-1(类固醇生成因子-1)。黄体生成素诱导快速而短暂的 分化癌组织中PR基因和蛋白(A、B亚型)的表达 大鼠排卵前卵泡的颗粒细胞。有针对性地扰乱 PR基因(PRKO)产生了不排卵的小鼠，从而证实了 PR和颗粒细胞在启动控制事件中的关键作用 排卵。黄体生成素诱导颗粒细胞PR的分子基础 仍然难以捉摸，但似乎涉及不同于或附加的机制 雌激素受体(ER)的激活。可供使用的 小鼠PR启动子和PR缺陷小鼠为我们提供了独特的 有机会扩大我们对PR激素调节的研究，并 确定PR在排卵生理中的功能作用。这 将通过1)分析小鼠PR启动子-报告构建来完成 2)用PRKO小鼠模型和 野生型小鼠鉴定和分析促黄体生成素和孕激素受体的诱导调节 基因和3)这些基因产物的功能与 特定的蛋白水解酶和激肽可能的活性和定位 与排卵过程相关的。在排卵前，黄体生成素激增 启动颗粒细胞的完全分子重新编程 对其终末分化和黄体细胞表达的影响 特定的基因。我们的特定基因，α2-巨球蛋白受 至少有两条不同的信号通路。其中包括的孤儿成员 核受体超家族SF-1和COUP-TF(鸡卵清蛋白) 上游刺激转录因子)以及至少一个成员 一类新的转录因子(信号转导和 转录激活子或Stat)，即Stat 5b。鉴于 SF-1的功能(COUP-TFS？)可受卵巢中促性腺激素的调节 细胞，Stat 5b被PRL激活。因此，我们处于独一无二的 能够确定Stat 5b如何与孤儿交互的职位 核受体调节α2M的表达。这些型号将 允许我们确定黄体生成素是如何调节诱导(PR)和激活的 核转录因子(SF-1)及其转导途径 促黄体生成素促进排卵和黄体生成的两个主要事件 哺乳动物的卵巢，它能敏锐地决定生育能力。

The luteinizing hormone (LH) surge initiates two processes unique to the vertebrate ovary-ovulation and luteinization. Both require the expression and activation of specific nuclear receptors. PR (progesterone receptor) and SF-1 (steroidogenic factor-1). LH induces the rapid but transient expression of PR mRNA and protein (A and B isoforms) in differentiated granulosa cells of rat preovulatory follicles. Targeted disruption of the PR gene (PRKO) generated mice that do not ovulate, thereby confirming the critical role of PR and granulosa cells in initiating events that control ovulation. The molecular basis by which LH induces PR in granulosa cells remain elusive but appears to involve mechanisms other than or in addition to activation of the estradiol receptor (ER). The availability of the mouse PR promoter and mice deficient in PR provides us with the unique opportunity to extend our studies on the hormonal regulation of PR and to determine the functional roles of PR in the physiology of ovulation. This will be accomplished by 1) analyzing mouse PR promoter-reporter constructs transfected into granulosa cells, 2) using the PRKO mouse model and wildtype mice to identify and analyze the induction of LH and Pr regulated genes and 3) relating the function of these gene products to the activities and localization of specific proteases and kinins likely associated with the ovulatory process. Prior to ovulation, the LH surge initiates the complete molecular reprogramming of granulosa cells leading to their terminal differentiation and the expression of luteal cell specific genes. Our specific genes, alpha2-macroglobulin is regulated by at least two distinct signaling pathways. These include orphan members of the nuclear receptor superfamily, SF-1 and COUP-TFs (chick ovalbumin upstream stimulatory-transcription factors) as well as at least one member of a novel class of transcription factors (signal transducers and activators of transcription or Stats), namely Stat 5b. Whereas the function of SF-1 (COUP-TFs?) can be regulated by gonadotropins in ovarian cells, Stat 5b is activated by PRL. Therefore, we are in the unique position of being able to determine how Stat 5b interacts with orphan nuclear receptors to regulate the expression of alpha2M. These models will allow us to determine how LH regulates the induction (PR) and activation (SF-1) of nuclear transcription factors and how these factors in turn mediate LH stimulation of ovulation and luteinization-two major events in the mammalian ovary that acutely determine fertility.