PEPTIDES AND REPRODUCTION

肽与繁殖

• 批准号: 2197007
• 负责人: WYLIE W. VALE
• 金额: $ 100.62万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2197007
• 关键词: biological signal transduction; gonadotropin releasing factor; hormone receptor; hormone regulation /control mechanism; inhibin; neuroendocrine system; peptide hormone; reproduction; biological signal transduction; gonadotropin releasing factor; hormone receptor; hormone regulation /control mechanism; inhibin; neuroendocrine system; peptide hormone; reproduction

This Program of 15 years explores the reproductive roles and signaling mechanisms of protein/peptide hormones and growth factors originally characterized by virtue of their neuroendocrine actions; focus is on inhibin and activin and their receptors and GnRH. Project 1 (Vale): Which discovered the first activin receptor during the current funding period will examine the nature and signaling of the complex between activin and the two types of activin receptors; will clone and characterize the inhibin receptors; and will study the regulation of the activin and inhibin receptors in the pituitary. Project 2 (C.Rivier): Will investigate the modulation of hypothalamic GnRH production by activin and inhibin and will continue to probe the interactions between the reproductive and immune systems. Project 3 (J.Rivier): Will deign conformationally constrained analogs of GnRH for biological and structural analyses and will continue to develop and provide potent antagonists for clinical studies. Project 4 (Fischer): Will design and produce recombinantly, mutated activins probe requirements for receptor recognition and signaling. Project 5 (Choe): Will use X-ray crystallography to solve the tertiary structure of activin-activin receptor(s) ectodomain complexes, activin- follistatin complexes and avidin-biotinylated GnRH complexes. Core 1: Provides administrative support. Core 2: Provides characterized polyclonal antisera towards activins, inhibins and their receptors and radioimmunoassays for pituitary and gonadal hormones. Core 3 (Fisher): Prepares recombinant proteins needed in large quantities and characterizes recombinant proteins with regards to primary sequence, arrangement of disulfide bridges and phosphorylation. Core 4 (Rivier): Prepares and characterizes synthetic peptides for use as antigens or biological studies. The program thus brings together a diversity of skills and approaches to address fundamental questions of neuroendocrine control and signaling. Because of the importance of GnRH, inhibin and activin in fertility control and the pathogenesis of reproductive and other disorders, it is likely that these basic studies will continue to yield practical benefits.

该计划15年探讨了生殖角色和信号传导 蛋白质/肽激素和生长因子的机制最初 以其神经内分泌作用的优点为特征；重点是 抑制素和激活素及其受体以及GNRH。 项目1（Vale）：在此期间发现了第一个激活素受体 当前的资金期将检查 激活素和两种类型的激活素受体之间的复合物；将要 克隆并表征抑制素受体；并将研究 垂体中激活素和抑制素受体的调节。 项目2（C. Rivier）：将研究下丘脑的调节 激活素和抑制素的GNRH产生，并将继续探测 生殖和免疫系统之间的相互作用。 项目3（J.Rivier）：将构象构成的类似物的类似物 GNRH进行生物学和结构分析，并将继续发展 并为临床研究提供有效的拮抗剂。 项目4（Fischer）：将重组设计和生产，突变 激活素探针对受体识别和信号传导的要求。 项目5（Choe）：将使用X射线晶体学来解决第三纪 活化素活性受体的结构（S）外生域复合物，激活素 - Follistatin复合物和Avidin-Biotinyly的GNRH复合物。 核心1：提供管理支持。 核心2：提供具有特征性的多克隆抗血清朝向激活素， 抑制剂及其受体以及垂体的放射免疫分子 性腺激素。 核心3（Fisher）：准备大量需要的重组蛋白 并以主序列为特征重组蛋白 二硫键和磷酸化的排列。 核心4（rivier）：准备并表征用于使用的合成肽 作为抗原或生物学研究。 因此，该计划汇集了各种技能和方法 解决神经内分泌控制和信号传导的基本问题。 由于GNRH的重要性，抑制素和刺激在生育方面 控制和生殖和其他疾病的发病机理，它是 这些基础研究可能会继续产生实用 好处。