The Role of Smads and AR in FSHbeta Gene Expression

描述(申请人提供)：卵泡刺激素的合成对包括人类在内的哺乳动物的正常生殖功能至关重要。虽然有相当多的证据表明激活素和雄激素等多肽和类固醇激素调节FSHBeta基因的转录，但这种调节的分子机制仍未阐明。由于目前尚不清楚激活素和雄激素如何影响FSHBeta基因的转录，我将研究Smad蛋白和雄激素受体(AR)在小鼠促性腺激素细胞系中调节小鼠FSHBeta基因的作用，并使用以下特定目的概述的转基因小鼠体内。特异目的1“确定Smads和/或AR是否调节LBT2细胞中FSHBeta基因的表达。特异目的2：研究Smads、AR和PBX/Prep同源域蛋白之间的相互作用。特异目的3：确定Smads和/或AR是否在体内调节小鼠垂体促性腺激素FSHβ基因的表达。

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.