Center for Reproductive Science and Medicine

项目总结(见说明)： 加州大学圣迭戈分校生殖科学和医学中心的目标是了解控制下丘脑-垂体-卵巢轴正常和紊乱功能的机制。这份申请书代表着我们29-33年的续期。我们的工作效率一直很高，有60篇论文 在为期4年的奖项中，发表了9篇，3年内提交了9篇。我们将继续为生殖科学做出新的、重大的贡献，整合多学科的临床、转化和基础研究，促进和加快将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，所有项目都有经验丰富的国际知名领导者参与。项目I(Pamela L.Mellon，PL)将解决垂体促性腺激素的激素控制问题，重点是激活素、促性腺激素释放激素和类固醇激素在体外和体内的调节。重点将是了解这些激素之间在控制转录过程中的协同和相互依赖。 永生化促性腺激素细胞模型，转基因小鼠，性早熟和多囊卵巢综合征小鼠模型。项目II(Jerrold M.Olefsky，PL)将在代谢控制在生育中的作用方面绘制新的领域。 体内/体外双重方法将阐明脂联素、SirT1和PPARy在调节生殖方面的作用机制，使用永生化的下丘脑GnRH分泌神经元和促性腺激素细胞、新的转基因小鼠和PCOS小鼠模型。项目III(R.Jeffrey Chang，PL)将描述 该中心的主要任务是研究与多囊卵巢综合征患者卵巢膜细胞过度分泌雄激素有关的特定因素的相对作用，并在人类卵巢培养系统中开展研究，探讨多囊卵巢综合征的基本机制。所有项目负责人都是中心其他组成部分的联合L，所有三个项目都包括非常有经验的调查团队。这些项目互动性很强， 协同，创造一个连贯的机械和翻译中心。管理核心为中心提供支持，提供丰富计划，并促进中心和SCCPIR计划之间的互动。SCCPIR人类卵巢组织库为美国国立卫生研究院资助的全国研究人员提供组织。

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.