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.
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 rat testicular follicle-stimulating hormone receptor (FSHR) affected signal transduction in rat testis membranes and cultured rat Sertoli cells. In order to define more precisely the peptide domains involved, we synthesized truncated peptide amides corresponding to FSHR residues 551-555 (KIAKR) and 650-653 (RKSH), respectively. These two regions were chosen since they contained a minimal structural motif present in G protein 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). Neither peptide inhibited binding of FSH to testis membrane receptors. Each peptide significantly reduced FSH-stimulated estradiol biosynthesis by intact cultured rat Sertoli cells. The same results were obtained with 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 nucleotide exchange in rat testis membranes. Our results indicate that interaction of FSH receptor with its associated G protein may involve relatively restricted peptide sequences, and include residues 551-555 (KIAKR) in the third cytoplasmic loop, and residues 650-653 (RKSH) in the carboxy-terminal cytoplasmic tail of the FSH receptor.
Grasso
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P
Department of Biochemistry and Molecular Biology, Albany Medical College A-10, NY 12208, USA.
Deziel
M R
MR
Reichert
L E
LE
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000737:chemistry; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000187:drug effects*; D012708:Sertoli Cells / Q000187:drug effects*
D010446:Peptide Fragments; D011962:Receptors, FSH; D005576:Colforsin; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D019204:GTP-Binding Proteins