ANDROGEN REGULATION OF GONADOTROPIN GENE EXPRESSION

我们将使用体外和体内模型系统来研究雄激素在垂体促性腺激素水平上调节促性腺激素基因表达的分子机制。L旨在阐明雄激素调节永生化促性腺激素细胞系卵泡刺激素β(FSHβ)和黄体生成素β(LHbeta)基因表达的机制(S)。为此，我们将研究雄激素的直接或间接作用是否被用来在促性腺激素水平上调节促性腺激素基因的表达，确定雄激素调节所需的FSHbeta3和LHbeta基因的上游元件，并检测雄激素受体与FSHbeta和LHbeta基因的这些已定义区域的结合。具体目的2是利用雄激素受体功能被特异性阻断的转基因小鼠，在体内确定雄激素受体在调节垂体促性腺激素FSHbeta和LHbeta基因表达中的作用。这些研究结果将阐明雄激素在垂体促性腺激素水平上调节促性腺激素基因表达的分子机制，从而为更深入地了解生殖激素反馈调控的分子机制提供依据。

We will examine the molecular mechanism through which androgens act at the level of the pituitary gonadotrope to regulate gonadotropin gene expression, using both in vitro and in vivo model systems. Specific Aim l is to elucidate the mechanism(s) of androgen regulation of follicle-stimulating hormone beta (FSHbeta) and luteinizing hormone beta (LHbeta) gene expression in an immortalized gonadotrope cell line. In this Aim, we will address whether direct or indirect actions of androgen are utilized to regulate gonadotropin gene expression at the level of the gonadotrope, identify upstream elements of the FSHbeta3 and LHbeta genes that are required for androgen regulation, and examine the binding of androgen receptor to these defined regions of the FSHbeta and LHbeta genes. Specific Aim 2 is to determine the role of androgen receptor in the regulation of FSHbeta and LHbeta gene expression within the pituitary gonadotrope in vivo using transgenic mice in which function of the androgen receptor has been blocked specifically within gonadotropes. The results of these studies will elucidate the molecular mechanisms through which androgens regulate gonadotropin gene expression at the level of the pituitary gonadotrope, thereby providing a more thorough understanding of the molecular mechanisms involved in steroid feedback regulation of reproduction.