Center for Reproductive Science and Medicine

项目总结（见说明）： 加州大学圣地亚哥分校生殖科学与医学中心的目标是了解下丘脑-垂体-卵巢轴正常和紊乱功能的机制。此应用程序代表我们29-33年的更新。我们的生产力一直很出色，有60篇论文 在4年的奖励中，3年内发表了9篇文章。我们将继续为生殖科学做出新的重大贡献，整合多学科临床，转化和基础研究，以促进和加速有前途的新发现转化为临床医学。我们提出了3个综合的，创新的研究项目，都与经验丰富，国际知名的领导人。项目I（Pamela L. Mellon，PL）将讨论垂体促性腺激素的激素控制，重点是体外和体内激活素、GnRH和类固醇激素的调节。重点将是了解这些激素之间的协同作用和相互依存关系，在控制转录， 模型永生化促性腺细胞、遗传修饰小鼠和性早熟和PCOS的小鼠模型。项目二（Jerrold M. Olefsky，PL）将绘制代谢控制在生育中作用的新领域。 体内/体外双重方法将阐明脂联素，SirT 1和PPARy在调节生殖中的作用机制，使用永生化的下丘脑GnRH分泌神经元和促性腺细胞，新型遗传修饰小鼠和PCOS小鼠模型。项目三（R. Jeffrey Chang，PL）将描述 与PCOS妇女卵巢卵泡膜细胞雄激素过量产生有关的特定因素的相对作用，并在人类卵巢培养系统中进行研究，解决PCOS的基本机制。所有项目负责人都担任中心其他组成部分的首席执行官，所有3个项目都包括经验丰富的调查员团队。这些项目具有高度互动性， 协同，创造一个连贯的机械和翻译中心。行政核心支持中心，提供强化计划，并促进中心和SCCPIR计划之间的互动。SCCPIR人类卵巢组织库为全国NIH资助的研究人员提供组织。

PROJECT SUMMARY (See instructions): The goal of the Center for Reproductive Science and Medicine at UCSD is to develop understanding of the mechanisms that govern normal and disordered function of the hypothalamic-pituitary-ovarian axis. This application represents our renewal for years 29-33. Our productivity has been outstanding with 60 papers published and 9 submitted in 3 years of a 4-year award. We will continue to produce novel, significant contributions to the reproductive sciences, integrating multidisciplinary clinical, translational, and basic research to facilitate and accelerate the translation of promising new discoveries into clinical medicine. We are proposing 3 integrated, innovative Research Projects, all with experienced, internationally renowned leaders. Project I (Pamela L. Mellon, PL) will address the hormonal control of the pituitary gonadotrope, focusing on regulation by activin, GnRH, and steroid hormones in vitro and in vivo. The emphasis will be on understanding the synergy and interdependence between these hormones in controlling transcription in model immortalized gonadotrope cells, genetically modified mice, and mouse models of precocious puberty and PCOS. Project II (Jerrold M. Olefsky, PL) will chart new territory in the role of metabolic control in fertility. A dual in vivo/in vitro approach will elucidate the mechanisms of adiponectin, SirT1, and PPARy actions in regulating reproduction, using immortalized hypothalamic GnRH-secreting neurons and gonadotrope cells, novel genetically modified mice, and mouse models of PCOS. Project III (R. Jeffrey Chang, PL) will delineate the relative roles of specific factors implicated in excess production of androgen by the ovarian theca cell in women with PCOS and undertake studies in human ovary culture systems, addressing fundamental mechanisms underlying PCOS. All Project Leaders serve as Co-l's on other components of the Center and all 3 projects include teams of very experienced investigators. The Projects are highly interactive and synergistic, creating a coherent mechanistic and translational Center. The Administrative Core supports the Center, provides the Enrichment Program, and facilitates interactions within the Center and the SCCPIR Program. The SCCPIR Human Ovary Tissue Bank provides tissue to NIH-funded investigators nation-wide.