HORMONAL CONTROL OF AROMATASE GENE EXPRESSION

芳香酶细胞色素P450的激素和组织特异性调控 (CyP19)基因对雌二醇的合成是必需的 女性生殖系统的功能。芳香酶的高效表达 卵巢颗粒细胞以cAMP依赖的方式受 多肽激素、促卵泡刺激素和促黄体生成素通过蛋白n-激酶A途径。在……里面 此外，芳香化酶在大鼠体内的表达是专一性的。 卵巢、睾丸和大脑。这份提案的重点是确定 顺式作用的DNA元件和反式作用因子 CAMP依赖性和组织特异性芳香化酶的表达 老鼠的卵巢。使用电泳迁移率变化分析以及 芳香酶瞬时转染卵巢颗粒细胞的研究 启动者CAT报告构建将使我能够确定 启动子和启动子的特定调控区域的功能 与这些启动子元件结合的蛋白质。的决定 组织特异性表达所需的基因组序列 芳香酶的研究将通过转基因小鼠的一代来进行。 从这些研究获得的结果将提供基本信息 关于大鼠芳香酶的转录调控 CAMP启动子并确定组织特异性所需的区域 芳香酶基因在体内的表达。

Hormonal and tissue-specific control of the aromatase cytochrome P450 (CYP 19) gene is obligatory for the synthesis of estradiol and proper function of the female reproductive system. Expression of aromatase by ovarian granulosa cells is regulated in a cAMp-dependent manner by the peptide hormones, fSH and LH via the protei n-kinase A pathway. In addition, expression of aromatase in the rat is exclusively localized to the ovary, testis and brain. This proposal focuses on identifying cis-acting DNA elements and trans-acting factors that mediate the cAMp-dependent as well as tissue-specific expression of aromatase in the rat ovary. Use of electrophoretic mobility shift assays as well as transient transfection of ovarian granulosa cells with aromatase promoter CAT reporter constructs will allow me to determine the function of specific regulatory regions of the promoter and the proteins that bind to these promoter elements. Determination of genomic sequences necessary for tissue-specific expression of aromatase will be investigated by generation of transgenic mice. Results obtained from these studies will provide basic information concerning the transcriptional regulation of the rat aromatase promoter by cAMP and identify the regions required for tissue-specific expression of the aromatase gene in vivo.