CENTER FOR STUDY OF REPRODUCTIVE BIOLOGY AND DISEASE

生殖生物学和疾病研究中心的目标将是加深对控制下丘脑-垂体-卵巢轴正常和紊乱功能的机制的理解。我们将继续在生殖科学方面做出新的重要贡献，整合多学科的临床和基础研究，促进和加快将有希望的新发现转化为临床医学。我们选择了五个创新研究项目，所有项目都有经验丰富的国际知名领导者参与。研究项目11将研究促性腺激素基因调控的分子机制，特别是对GnRH和激活素/卵泡抑素系统的反应及其相互作用。研究项目12将在卵母细胞在卵泡成熟中的作用方面开辟新的领域，研究GDF-9在大鼠和人类卵巢中的作用。研究项目13将提供对促性腺激素释放激素信号转导级联的详细分子理解。分析将包括G蛋白在α和β亚基中的作用，MAP激酶和ras的作用，以及GnRH在促性腺激素中各种作用的不同使用信号通路。研究项目14将调查骨形态发生蛋白在卵巢生理中的作用，骨形态发生蛋白是转化生长因子-β超家族的成员。重点将放在测试新的假设上，即BMP是黄体化抑制剂，它们的活动受卵泡抑素调节。分析将包括培养的大鼠和人类颗粒细胞以及体内的大鼠。研究项目15将集中在正常妇女和多细胞卵巢综合征患者体内卵巢颗粒和膜室内胰岛素对黄体生成素释放和类固醇合成的内分泌控制的影响。提出了两个封闭核心：管理核心和重组蛋白核心。行政核心将提供行政、财政、规划和会议服务，并管理浓缩计划。重组蛋白质核心将满足研究项目对蛋白质和抗体的生产、纯化和表征的需求，这些需求在其他地方是无法获得的。我们预计，这个综合研究中心将产生一系列发现，提供对控制生殖功能的分子、细胞和系统的全面了解，从而改进疾病的治疗。

The goal of the Center for the Study of Reproductive Biology and Disease will be do develop understanding of the mechanisms which govern normal and disordered function of the hypothalamic-pituitary- ovarian axis. We will continue to produce novel and important contributions os the reproductive sciences, integrating multi- disciplinary clinical and basic research to facilitate and accelerate the translation of promising new discoveries into clinical medicine. We have chosen five innovative research projects, all with experienced, internationally renowned leaders. Research project 11 will investigate the molecular mechanisms of gene regulation in the gonadotrope with specific focus on responses to GnRH and the activin/follistatin system and their interactions. Research project 12 will chart new territory in the role of the oocyte in follicular maturation studying GDF-9 in both rat and human ovaries. Research Project 13 will provide detailed molecular understanding of the signal transduction cascade of GnRH. Analyses will include the roles of G proteins both alpha and Betagamma subunits, the role of MAP kinase and ras, and differential use signaling pathways for various actions of GnRH in the gonadotrope. Research Project 14 will investigate the roles of the Bone Morphogenetic Proteins, members of the TGF-Beta superfamily, in ovarian physiology. Emphasis will be placed on testing the new hypothesis that BMPs are luteinization inhibitors and their activities are regulated by follistatin. Analyses will include cultured rat and human granulosa cells and rats in vivo. Research project 15 will focus on the influence of insulin in the endocrine control of LH release and steroid synthesis by the ovarian granulosa and theca compartments in vivo in normal women and patients with polycytic ovary syndrome. Two closed Cored are proposed: the Administrative Core and the Recombinant Protein Core. The Administrative Core will provide administrative, fiscal, planning and meeting services and administer the Enrichment Program. The Recombinant Protein Core will meet the needs of the Research Projects for production, purification and characterization of proteins and antibodies that are unavailable elsewhere. We envision that this integrated research Center will generate a repertoire of discoveries that will provide a comprehensive understanding of the molecules, cells, and systems involved in controlling reproductive function, leading to improved treatment of disease.