ROLE OF SF1 AND DAX1 IN OVARIAN FUNCTION

FSH主要通过蛋白激酶A途径发挥作用， 卵泡发育和功能。最近的研究表明， FSH/cAMP通路与一组转录因子（SF-1，DAX-1） 控制卵巢中的靶基因。SF-1和DAX-1是孤儿核 受体，发挥关键作用的发展和功能， 肾上腺、性腺和垂体促性腺激素。SF-1基因敲除 阻止这些器官的发育，SF-1反应元件具有 在许多不同的卵巢基因的启动子中被鉴定。突变 X连锁DAX-1基因导致肾上腺发育不全综合征 先天性的它的特点是缺乏成年区的 肾上腺皮质伴低促性腺激素性腺功能减退症伴明显正常 睾丸间质细胞功能DAX-1的复制导致性逆转 在遗传男性中，DAX-1被假定为促进卵巢 发展我们已经证明，DAX-1调节SF-1的作用，并发挥作用。 在卵巢发育和功能中起重要作用。我们已经证明，DAX- 1调节SF-1的作用，并假设DAX-1和SF-1的平衡 在卵巢中的表达调节其发育，随后， 各种靶基因如α-肾上腺素和类固醇生成基因的功能 酶基因我们提出了一个综合组在体外和体内 研究进一步确定SF-1和DAX-1在卵巢中的功能。 有三个具体目标：1）检查cAMP 和SF-1通路相互作用调节卵巢基因。我们假设 转录辅因子，如CBP，提供了一个基础， FSH信号通路与核受体SF-1; 2） 确定DAX-1对SF-1介导的 不同卵巢靶基因的转录。我们假设DAX-1 启动子将作为SF-1应答的代表性实例进行研究。 DAX-1差异调节的基因; 3）为了确定DAX-1的表达， DAX-1基因靶向缺失和过表达对卵巢癌基因表达影响 表情这些研究将在体内测试DAX-1是否在 卵巢发育和卵巢基因表达的调控。

FSH, acting primarily through the protein kinase A pathway, regulates follicular development and function. Recent studies reveal convergence of the FSH/cAMP pathway with a group of transcription factors (SF-1, DAX-1) that control target genes in the ovary. SF-1 and DAX-1 are orphan nuclear receptors that play a key role in the development and function of the adrenal, gonads, and pituitary gonadotropes. A gene knock-out of SF-1 prevents the development of these organs, and SF-1 response elements have been identified in promoters of many different ovarian genes. Mutation of the X-linked DAX-1 gene causes the syndrome of adrenal hypoplasia congenital. It is characterized by the absence of the adult zone of the adrenal cortex with hypogonadotropic hypogonadism with apparently normal testicular Leydig cell function. Duplication of DAX-1 causes sex reversal in genetic males, and DAX-1 has been postulated to foster ovarian development. We have shown that DAX-1 modulates SF-1 action and play a critical role in ovarian development and function. We have shown that DAX- 1 modulates SF-1 action and hypothesize that the balance of DAX-1 and SF-1 expression in the ovary regulates its development, and subsequently, the function of various target genes like inhibin-alpha and steroidogenic enzyme genes. We propose an integrated group of in vitro and in vivo studies to further define the functions of SF-1 and DAX-1 in the ovary. There are three specific aims: 1) To examine mechanisms by which the cAMP and SF-1 pathways interact to regulate ovarian genes. We hypothesize that transcriptional co-factors, such as CBP, provide a basis for convergence of the FSH signaling pathway with the nuclear receptor, SF-1; 2) To determine the basis of divergent effects of DAX-1 on SF-1-mediated transcription of different ovarian target genes. We hypothesize that DAX-1 promoters will be studied as representative examples of SF-1 responsive genes that are regulated differentially by DAX-1; 3) To determine the effect of targeted deletion and over-expression of DAX-1 on ovarian gene expression. These studies will test in vivo whether DAX-1 plays a role in ovarian development and in the regulation of ovarian gene expression.