HUMAN FSH-RECEPTOR BINDING INHIBITORS

A.候选 博士丹尼尔W.李获得了医学博士学位。1982年毕业，并担任董事会 在内科和也在亚专科认证 内分泌和代谢。 他目前是一名 1988年1月11日至1988年1月11日期间的国家研究服务奖（NIH） 10/31/91. 本提案适用于临床研究者 奖励（5年），以支持他作为一个 独立临床研究者。 B。研究 本项目的主要目标是纯化和研究一种 先前鉴定的大分子量FSH受体结合 来自人卵泡液（hFF）的FSH-BI抑制剂，其可以 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 来自hFF人FSHBI，2）生物学表征hFSH-BI， 研究其激动剂/拮抗剂特性以及其作用 在已知对FSH有反应的各种系统上，3）开发一种测定方法 为了测量hFF中的hFSH-BI，4）测定其细胞， 来源，5）克隆和测序FSH-BI和6）研究FSH-BI 在不同成熟度的卵泡中合成和表达。 C.环境 博士利奥·E Reichert，Jr.，生物化学教授和赞助商， 长期以来一直对促性腺激素感兴趣， 受体化学和作用机制以及 影响受体-受体相互作用（见参考文献）。 他 实验室装备精良，以支持研究方向 该项目的主要目标是需要蛋白质和肽 FSH-BI分离、通过放射受体表征和 放射免疫测定和组织培养。 此外该 现代化的生物化学系的设施将是 可用于开展研究。 主席的 凯文·戴维斯博士，是一位公认的 生物学家，并与约翰杰弗里博士（见简历），将 提供所需的相关领域的专业知识， research.

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.