CAMP DEPENDENT TRANSCRIPTIONAL REGULATION OF CYP51

CYP51 的 CAMP 依赖性转录调控

• 批准号: 2908312
• 负责人: MICHAEL R WATERMAN
• 金额: $ 4.03万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2908312
• 关键词: adrenal glands; cholesterol; corticosteroids; cyclic AMP; cytochrome P450; gel mobility shift assay; genetic transcription; germ cells; immunoprecipitation; lipid metabolism; northern blottings; reporter genes; spermatogenesis; tissue /cell culture; transfection

The long term goal of collaborative research between the P.I. and the foreign collaborator is to determine the role of the high level expression of CYP51 (lanosterol 14alpha-demethylase cytochrome P450) in haploid, postmeiotic germ cells. This FIRCA proposal addresses a portion of this overall goal and will lead to an understanding of the biochemical mechanisms involved in cAMP-dependent transcription of CYP51 in somatic and germ cells. The specific aims for the proposed three years are to study cAMP- dependent transcriptional regulation of CYP51 in steroidogenic (somatic) cells (Aim 1) and in haploid germ cells (Aim 2). The parent grant (DK28350) addresses ACTH (cAMP)-dependent transcription of genes (particularly encoding P450 enzymes) in the adrenal cortex, a process essential for maintenance of optimal steroidogenic capacity. Aim 1 is an extension of DK28350 and will establish whether a link between cAMP-dependent transcription of genes encoding steroidogenic P450s (cholesterol metabolism) and CYP51 (cholesterol biosynthesis) exists in the adrenal cortex. It seems likely that two different signalling pathways, oxysterol/SRE and cAMP/CRE, interact to control CYP51 levels in steroidogenic cells. Preliminary data indicates that CYP51 is transcriptionally regulated by cAMP in haploid germ cells. Aim 2 is a new direction for studies in DK28350 and will establish the biochemical basis of this postmeiotic transcriptional regulation. Results from these studies will provide a more detailed understanding of steroid hormone biosynthesis which is a major path of cholesterol metabolism and of spermatogenesis in male reproduction.

P.I.之间合作研究的长期目标。国外合作者的目标是确定CYP 51（羊毛甾醇14 α-去甲基酶细胞色素P450）在单倍体、减数分裂后生殖细胞中的高水平表达的作用。 该FIRCA提案解决了这一总体目标的一部分，并将导致对体细胞和生殖细胞中cAMP依赖性CYP 51转录所涉及的生化机制的理解。拟议三年的具体目标是研究类固醇生成（体细胞）细胞（目标1）和单倍体生殖细胞（目标2）中CYP 51的cAMP依赖性转录调控。 母基金（DK 28350）致力于肾上腺皮质中基因（特别是编码P450酶）的促肾上腺皮质激素（cAMP）依赖性转录，这是维持最佳类固醇生成能力所必需的过程。 目的1是DK28350的延伸，将确定肾上腺皮质中编码类固醇生成P450（胆固醇代谢）和CYP 51（胆固醇生物合成）的基因的cAMP依赖性转录之间是否存在联系。 似乎有可能是两种不同的信号通路，氧化固醇/SRE和cAMP/CRE，相互作用，以控制类固醇生成细胞中的CYP 51水平。初步数据表明，CYP 51在单倍体生殖细胞中受cAMP的转录调控。 目的2为DK28350基因的研究开辟了新的方向，并将为DK28350减数分裂后的转录调控奠定生物化学基础。 这些研究的结果将提供一个更详细的了解类固醇激素的生物合成，这是一个主要的途径胆固醇代谢和精子发生在男性生殖。