The Role of Smads and AR in FSHbeta Gene Expression

描述（由申请人提供）：FSH的合成对于哺乳动物（包括人类）的正常生殖功能至关重要。虽然有相当多的证据表明，肽和性类固醇激素，如激活素和雄激素调节FSH β基因的转录，这种调节的分子机制仍有待阐明。由于目前尚不清楚激活素和雄激素如何影响FSH β基因的转录，我将研究Smad蛋白和雄激素受体（AR）在小鼠促性腺细胞系和体内使用转基因小鼠中调节小鼠FSH β基因的作用，如以下具体目标所述。具体目的1”确定Smads和/或AR是否调节LBT 2细胞中的FSH β基因表达。具体目标2：表征Smads、AR和Pbx/Prep同源结构域蛋白之间的相互作用。具体目标3：确定Smads和/或AR是否在体内调节小鼠垂体促性腺激素中FSH β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.