The overall objective of this project continues understanding at the molecular level of the interaction the process of signal transduction. FSH receptor will testis by procedures developed during the recent period of project support. The receptor will be partially sequenced to allow preparation of cDNA probes with a view towards cloning of the receptor. Receptor functionality will be confirmed through use of reconstitution experiments. We will utilize enzymic and/or chemical fragmentation of the receptor, together with microsequencing, to identify regions of the receptor required for interaction with FSH. The role of carbohydrates in receptor function will be studied, as will be a possible role of phosphorylation in receptor signal transduction. The significance of the recently observed thioredoxin (protein disulfide isomerase) activity of FSH in terms of receptor activation will be probed, as will a possible function of the FSH receptor as a modulator of calcium ion transport into Sertoli cells (calcium gating effect). In support of the overall program, polyclonal and/or monoclonal antibodies will be raised against the receptor and fragments thereof. A variety of other studies are proposed, directed toward understanding FSH receptor interaction and signal transduction, which will be undertaken as circumstances dictate.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD013938-14
Application #
3312383
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1979-09-01
Project End
1996-01-31
Budget Start
1992-02-01
Budget End
1993-01-31
Support Year
14
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Albany Medical College
Department
Type
Schools of Medicine
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12208
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
Grasso, P; Rozhavskaya, M; Reichert Jr, L E (1997) A synthetic peptide corresponding to amino acid residues 34 to 37 of human follicle-stimulating hormone beta-subunit accelerates the onset of puberty in male and female mice. Endocrinology 138:4215-9
Grasso, P (1996) Functional reconstitution of detergent-solubilized bovine calf testis luteinizing hormone/chorionic gonadotropin receptor into phospholipid vesicles. Recept Signal Transduct 6:53-62
Grasso, P; Reichert Jr, L E (1996) In vivo effects of follicle-stimulating hormone-related synthetic peptides on the mouse estrous cycle. Endocrinology 137:5370-5
Grasso, P (1996) A synthetic peptide representing residues 7 to 21 of human luteinizing hormone beta-subunit binds calcium, facilitates calcium uptake by liposomes and possesses sequence similarity to calcium-binding domains of calmodulin. Regul Pept 65:109-14
Leng, N; Grasso, P; Reichert Jr, L E (1996) D-amino acid substitution of residues 32 to 46 of the glycoprotein hormone common alpha-subunit: development of a synthetic glycoprotein hormone antagonist. Pept Res 9:188-94
Grasso, P; Deziel, M R; Reichert Jr, L E (1995) Synthetic peptides corresponding to residues 551 to 555 and 650 to 653 of the rat testicular follicle-stimulating hormone (FSH) receptor are sufficient for post-receptor modulation of Sertoli cell responsiveness to FSH stimulation. Regul Pept 60:177-83
Grasso, P; Leng, N; Reichert Jr, L E (1995) A synthetic peptide corresponding to residues 645-653 in the carboxyl terminal cytoplasmic domain of the rat testicular follicle stimulating hormone receptor modulates G protein coupled-receptor signaling in rat testis membranes and in intact cultured rat Mol Cell Endocrinol 108:43-50
Leng, N; Dattatreyamurty, B; Reichert Jr, L E (1995) Identification of amino acid residues 300-315 of the rat FSH receptor as a hormone binding domain: evidence for its interaction with specific regions of FSH beta-subunit. Biochem Biophys Res Commun 210:392-9
Grasso, P; Deziel, M R; Reichert Jr, L E (1995) Selective effects of charge on G protein activation by FSH-receptor residues 551-555 and 650-653. Pept Res 8:278-84

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