SYNTHETIC PEPTIDES CORRESPONDING TO RESIDUE-551 TO RESIDUE-555 AND RESIDUE-650 TO RESIDUE-653 OF THE RAT TESTICULAR FOLLICLE-STIMULATING-HORMONE (FSH) RECEPTOR ARE SUFFICIENT FOR POSTRECEPTOR MODULATION OF SERTOLI-CELL RESPONSIVENESS TO FSH STIMULATION

We have recently demonstrated that synthetic peptides corresponding to the third cytoplasmic (3i) loop (residues 533 to 555) and a region in the carboxy-terminal cytoplasmic tail (residues 645 to 653) of the ra t testicular follicle-stimulating hormone receptor (FSHR) affected sig nal transduction in rat testis membranes and cultured rat Sertoli cell s. In order to define more precisely the peptide domains involved, we synthesized truncated peptide amides corresponding to FSHR residues 55 1-555 (KIAKR) and 650-653 (RKSH), respectively. These two regions were chosen since they contained a minimal structural motif present in G p rotein activator regions of several other G protein-coupled receptors (i.e., B-X-X-B-B or B-B-X-B, B representing a basic amino acid). Neith er peptide inhibited binding of FSH to testis membrane receptors. Each peptide significantly reduced FSH-stimulated estradiol biosynthesis b y intact cultured rat Sertoli cells. The same results were obtained wi th streptolysin O-permeabilized Sertoli cells. No effect was noted on forskolin-induced steroidogenesis, indicating that the peptide effects were not due to interaction with adenylyl cyclase. Each peptide amide , however, induced concentration-dependent increases in guanine nucleo tide exchange in rat testis membranes. Our results indicate that inter action of FSH receptor with its associated G protein may involve relat ively restricted peptide sequences, and include residues 551-555 (KIAK R) in the third cytoplasmic loop, and residues 650-653 (RKSH) in the c arboxy-terminal cytoplasmic tail of the FSH receptor.