HORMONAL CONTROL OF AROMATASE GENE EXPRESSION

芳香酶基因表达的激素控制

• 批准号: 2658086
• 负责人: DIANA L CARLONE
• 金额: $ 0.71万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2658086
• 关键词: aromatase; follicle stimulating hormone; gel mobility shift assay; gene expression; genetic promoter element; genetic regulatory element; genetically modified animals; hormone regulation /control mechanism; laboratory mouse; laboratory rat; luteinizing hormone; transcription factor; transfection

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.

芳香化酶细胞色素P450的激素和组织特异性控制 (CYP 19）基因是必需的合成雌二醇和适当的 女性生殖系统的功能。芳香化酶的表达 卵巢颗粒细胞以cAMP依赖的方式受到 通过蛋白激酶A途径调节肽激素、fSH和LH。在 此外，大鼠中芳香化酶的表达仅局限于 卵巢睾丸和大脑该建议的重点是确定 顺式作用DNA元件和反式作用因子，介导 芳香化酶的cAMP依赖性和组织特异性表达， 大鼠卵巢。使用电泳迁移率变动分析以及 用芳香化酶瞬时转染卵巢颗粒细胞 启动子CAT报告构建体将允许我确定 启动子的特异性调控区的功能， 与这些启动子元件结合的蛋白质。测定 组织特异性表达所必需的基因组序列 将通过产生转基因小鼠来研究芳香酶。 从这些研究中获得的结果将提供基本信息 关于大鼠芳香化酶的转录调节 启动子的cAMP，并确定所需的区域，组织特异性 芳香化酶基因的体内表达。