HUMAN FSH-RECEPTOR BINDING INHIBITORS

答：候选人 丹尼尔·W·李博士于1982年获得医学博士学位，现为董事会成员 有内科证书，也有专科证书 内分泌学和新陈代谢。他目前是一个获奖者 1988年11月1日期间国家研究服务奖(NIH)- 10/31/91.目前的建议是设立一名临床调查员 奖励(5年)，以支持他作为一名 独立的临床调查员。 B.研究 本项目的主要目标是提纯和研究一种 先前发现的大分子FSH受体结合 来自人卵泡液(HFF)的抑制物(FSH-BI)，可能是 参与卵泡的自分泌或旁分泌调节 成熟。该项目的具体目标是：1)净化 HFF来源的人FSHBI，2)hFSH-BI生物学特性 研究其激动剂/拮抗剂的性质及其作用 在已知的对FSH反应的各种系统上，3)开发一种分析方法 用于测量HFF中的hFSH-BI，4)测定其细胞 5)FSH-BI的克隆和测序及6)FSH-BI的研究 在不同成熟度的卵泡中合成和表达。 C.环境 生物化学教授和赞助商小利奥·E·赖切特博士， 长期以来一直对促性腺激素和 受体化学及其作用机制和影响因素 影响激素-受体的相互作用(见参考文献)。他的 实验室设备齐全，可以支持针对以下目标的研究 需要蛋白质和多肽的项目的主要目标 FSH-BI的分离、放射受体及鉴定 放射免疫分析和组织培养。此外， 现代化生物化学系的设施将是 可用于进行研究。该委员会的主席 科室的凯尔文·戴维斯博士是公认的分子 生物学家和约翰·杰弗里博士(见简历)，威尔 提供建议的相关领域所需的专业知识 研究。

A. The Candidate Dr. Daniel W. Lee obtained the M.D. degree in 1982 and is Board Certified in Internal Medicine and also in the subspecialty of Endocrinology and Metabolism. He is currently the recipient of a National Research Service Award (NIH) for the period 11/01/88 - 10/31/91. The present proposal is for a Clinical Investigator Award (5 years) to support his further development as an independent clinical investigator. B. The Research The principle goal of this project is to purify and study a previously identified large molecular weight FSH-receptor binding inhibitor (FSH-BI) from human follicular fluid (hFF) which may be involved in the autocrine or paracrine regulation of follicular maturation. The specific goals of the project are to: 1) purify human FSHBI from hFF, 2) biologically characterize hFSH-BI by studying its agonist/antagonist properties as well as its effects on various systems known to respond to FSH, 3) develop an assay for measurement of hFSH-BI in hFF, 4) determine its cell of origin, 5) clone and sequence FSH-BI and 6) study FSH-BI synthesis and expression in follicles of varying maturity. C. The Environment Dr. Leo E. Reichert, Jr., Professor of Biochemistry and Sponsor, has had a long standing interest in gonadotropin hormone and receptor chemistry and mechanism of action and in factors that affect the hormone-receptor interaction (see bibliography). His laboratory is well equipped to support research directed toward the principle goals of the project requiring protein and peptide isolation, characterization of FSH-BI by radioreceptor and radioimmunoassays and by tissue culture. In addition, the facilities of a modern Department of Biochemistry will be available for conduct of the research. The Chairman of the Department, Dr. Kelvin Davies, is a recognized molecular biologist and together with Dr. John Jeffrey (see CV), will provide the expertise needed in related areas of proposed research.