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Title: 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 Sertoli cells. Author: Grasso P, Leng N, Reichert LE. Journal: Mol Cell Endocrinol; 1995 Feb 27; 108(1-2):43-50. PubMed ID: 7758839. Abstract: We examined the involvement of the carboxyl terminal cytoplasmic domain (residues 645-653) of the rat testicular FSH receptor in FSH signal transduction utilizing light membranes prepared from immature rat testes, intact cultured rat Sertoli cells, and a synthetic peptide approach. This region of the FSH receptor was selected because of its structural similarity to receptor-G protein contact sites identified in other G protein-coupled receptors. FSHR- (645-653) peptide amide promoted guanine nucleotide exchange in rat testis membranes, presumably via its interaction with membrane-associated G protein, but did not inhibit FSH binding to testis membrane receptors. When incubated with intact cultured Sertoli cells from immature rat testes, FSHR- (645-653) peptide amide consistently and significantly stimulated basal cAMP and estradiol biosynthesis. The peptide had no effect on forskolin stimulation of cAMP and estradiol, but inhibited FSH stimulation of each. FSH binding to receptor was unaffected by the peptide, these results suggest peptide interaction with receptor-associated G protein. The effects of FSHR- (645-653) peptide amide on FSH-stimulated estradiol biosynthesis were prevented by pretreating Sertoli cells with phenylarsine oxide, an inhibitor of FSH receptor internalization. These results suggest that peptide effects in intact Sertoli cells were related to peptide entry into the cell, presumably during receptor-mediated endocytosis of FSH, or by diffusion. Synthetic peptide amides not satisfying structural criteria for G protein coupling had no effect on either guanine nucleotide exchange or estradiol biosynthesis, even at concentrations significantly higher than used for FSHR- (645-653) peptide amide.(ABSTRACT TRUNCATED AT 250 WORDS)[Abstract] [Full Text] [Related] [New Search]