ACTIONS OF ESTROGEN IN MATURING GRAAFIAN FOLLICLES

描述（改编自研究者摘要）：这是一份修订版 竞争更新应用程序，以调查控制机制 发育中的Graafian卵泡内的类固醇生成。 私家侦探具有 发现了两个关键基因的协同激素调节， 用于固醇代谢，即低密度脂蛋白（LDL）受体， 类固醇生成急性调节蛋白（星星）。 这两个功能 互补基因对调节卵巢类固醇生成至关重要， 低密度脂蛋白受体作为传递细胞外 胆固醇进入颗粒黄体细胞，星星充当 限速转运蛋白，将固醇底物转运到 线粒体胆固醇侧链裂解酶复合物。 私家侦探具有 发现促性腺激素、促卵泡激素（FSH）和 卵泡内生长因子、胰岛素样生长因子1（IGF-1） 产生8-20倍的协同刺激， LDL受体和星星mRNA的表达。 这项建议涉及 这种协同作用的机制。 具体的假设是 研究结果表明：（1）LDL受体基因和星星基因协同表达 2）FSH和IGF-1协同作用 通过扩增刺激LDL受体和星星mRNA表达增加 蛋白激酶A细胞内信号通路的影响; 3）FSH和IGF-1 诱导单个颗粒细胞LDL受体和星星基因表达 细胞水平，通过扩增每种基因转录物表达的量， 颗粒细胞和/或通过增加颗粒细胞表达 可测量的固醇调节基因转录物; 4）FSH和IGF-1增加 特异性LDL受体和星星基因转录起始速率，或 减少特异性mRNA降解（或两者）。 这些研究预计将 揭示了垂体激素（FSH）和 生长因子（IGF-1）单独或协同作用于卵巢细胞 群体和单个类固醇生成颗粒细胞，以控制 关键基因的协同表达和协同扩增， 直接进行类固醇合成。

DESCRIPTION (Adapted from the Investigator's Abstract): This is an amended competing renewal application to investigate the mechanisms controlling steroidogenesis within developing Graafian follicles. The P.I. has discovered synergistic hormonal regulation of two critical genes responsible for sterol metabolism, namely, low density lipoprotein (LDL) receptor and steroidogenic acute regulatory protein (StAR). These two functionally complementary genes are critical to regulated ovarian steroidogenesis, since the LDL receptor serves as the primary gateway for delivering extracellular cholesterol into the granulosa-luteal cell, and StAR acts as the rate-limiting transporter protein to convey sterol substrate to the inner mitochondrial cholesterol side-chain cleavage enzyme complex. The P.I. has found that the gonadotropin, follicle stimulating hormone (FSH), and the intrafollicular growth factor, insulin like growth factor 1 (IGF-1) together produce a synergistic stimulation of 8-20 fold in the enhancement of expression of LDL receptor and StAR mRNA. This proposal concerns the mechanisms of this synergistic action. The specific hypotheses to be investigated are: 1) LDL-receptor and StAR genes are expressed coordinately over time throughout the pig estrous cycle; 2) FSH and IGF-1 synergistically stimulate increased LDL receptor and StAR mRNA expression via amplification of the protein kinase A intracellular signaling pathway; 3) FSH and IGF-1 induce expression of LDL receptor and StAR genes at the single granulosa cell level by amplifying the amount of each gene transcript expressed per granulosa cell and/or by increasing the number of granulosa cells expressing measurable sterol-regulatory gene transcripts; 4) FSH and IGF-1 increase specific LDL-receptor and StAR gene transcriptional initiation rates or decrease specific mRNA degradation (or both). These studies are expected to reveal fundamental mechanisms by which a pituitary hormone (FSH) and the growth factor (IGF-1) act either alone or in concert on ovarian cell populations and on single steroidogenic granulosa cells to control the coordinated expression and synergistic amplification of pivotal genes that direct overall steroidogenesis.