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.
| Alouf, C A; Reichert Jr, L E; Kellom, T A et al. (1997) Cultured human granulosa cells secrete a follicle stimulating hormone receptor-binding inhibitor. Hum Reprod 12:2735-40 |
| Lee, D W; Grasso, P; Leng, N et al. (1995) A decapeptide corresponding to the partial amino acid sequence of a high molecular weight human FSH receptor-binding inhibitor is a specific inhibitor of FSH binding. Pept Res 8:171-7 |
| Figge, J; Leinung, M; Goodman, A D et al. (1994) The clinical evaluation of patients with subclinical hyperthyroidism and free triiodothyronine (free T3) toxicosis. Am J Med 96:229-34 |
| Lee, D W; Grasso, P; Dattatreyamurty, B et al. (1993) Purification of a high molecular weight follicle-stimulating hormone receptor-binding inhibitor from human follicular fluid. J Clin Endocrinol Metab 77:163-8 |
