The Role of Smads and AR in FSHbeta Gene Expression

Smads 和 AR 在 FSHbeta 基因表达中的作用

• 批准号: 6926980
• 负责人: Varykina G Thackray
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6926980
• 关键词: DNA binding protein; activins; androgen receptor; biological signal transduction; follicle stimulating hormone; gene expression; gene targeting; genetic regulation; genetically modified animals; gonadotropins; immunoprecipitation; laboratory mouse; postdoctoral investigator; protein localization; protein protein interaction; protein structure function; western blottings

DESCRIPTION (provided by applicant): Synthesis of FSH is critical for normal reproductive function in mammals, including humans. Although there is considerable evidence that peptide and sex steroid hormones such as activin and androgens regulate transcription of the FSHBeta gene, the molecular mechanisms of this regulation remain to be elucidated. Since it is not clear how activin and androgens influence the transcription of the FSHBeta gene, I will investigate the role of Smad proteins and the androgen receptor (AR) in the regulation of the mouse FSHBeta gene in a mouse gonadotrope cell line and in vivo using transgenic mice as outlined in the following specific aims. Specific Aim 1" Determine whether Smads and/or AR modulate FSHBeta gene expression in LBT2 cells. Specific Aim 2: Characterize the interactions among Smads, AR, and Pbx/Prep homeodomain Proteins. Specific Aim 3: Determine whether Smads and/or AR regulate FSH Beta gene expression in mouse pituitary gonadotropes in vivo.

描述（由申请人提供）：FSH的合成对于包括人类在内的哺乳动物中的正常生殖功能至关重要。尽管有大量证据表明，肽和性类固醇激素（例如激活素和雄激素）调节FSHBETA基因的转录，但该调节的分子机制仍有待阐明。由于尚不清楚激活素和雄激素如何影响FSHBETA基因的转录，因此我将研究SMAD蛋白质和雄激素受体（AR）在小鼠贡献细胞系中小鼠FSHBETA基因调节中的作用，并在以下特定目标中使用转基因小鼠在体内使用体内小鼠。具体目标1“确定SMADS和/或AR是否调节LBT2细胞中的FSHBETA基因表达。具体目标2：表征SMADS，AR和PBX/PREP PREP HOMEDOMAIN蛋白之间的相互作用。具体目的3：确定SMADS和/或AR AR调节FSH Beta基因在小鼠垂体刺斑gonadodotropes中是否调节FSH Beta基因。