ANDROGEN REGULATION OF GONADOTROPIN GENE EXPRESSION

我们将研究雄激素在垂体促性腺激素水平调节促性腺激素基因表达的分子机制，使用体外和体内模型系统。具体目的1是阐明雄激素调节永生化促性腺细胞系中促卵泡激素β（FSH β）和促黄体激素β（LH β）基因表达的机制。在这个目标中，我们将解决雄激素的直接或间接作用是否被用来调节促性腺激素基因的表达在促性腺激素的水平，确定上游元素的FSH β 3和LH β基因所需的雄激素调节，并检查雄激素受体的结合这些定义区域的FSH β和LH β基因。具体目的2是使用转基因小鼠（其中雄激素受体的功能在促性腺激素细胞内被特异性阻断），确定雄激素受体在体内垂体促性腺激素细胞内FSH β和LH β基因表达调节中的作用。这些研究的结果将阐明雄激素调节垂体促性腺激素水平的促性腺激素基因表达的分子机制，从而提供了一个更深入的了解类固醇反馈调节生殖的分子机制。

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.