Peptides of the growth hormone-releasing hormone family

Abstract

Growth hormone-releasing hormone (GHRH) belongs to a family of peptides expressed at high levels in the brain and digestive system of mammals. We have identified GHRH mRNA and peptide in rat and human germ cells, and detected a GHRH receptor mRNA in Sertoli cells. GHRH treatment of cultured Sertoli cells results in accumulation of cAMP and increased expression ofc-fos and stem cell factor (SCF), two factors critical for normal germ cell development. The current study was designed to localize within testis the transcription of other members of the GHRH family, and their receptors, and to determine if they also stimulate SCF. RNAs from separated testicular cells were amplified by comparative reverse transcription-polymerase chain reaction (RT-PCR). Southern blot analysis of the PCR products verified the presence of five GHRH family peptide and receptor transcripts in distinct testicular cell types. Transcripts encoding VIP and glucagon, and the receptors for pituitary adenylate cyclase activating peptide (PACAP) and glucagon, were detected predominantly in Leydig cells. In contrast, expression of GHRH, PACAP, secretin, and secretin receptor predominated in germ cells. Receptors for GHRH and VIP were expressed equally in all testicular cell types. To determine if, like GHRH, any of these other peptides activate Sertoli cell expression of SCF, primary Sertoli cell cultures were treated for 4-6 h with 10 or 100 nM of each individual factor. There was no consistent stimulation of SCF mRNA by VIP, PACAP, glucagon, or secretin. Differential expression of these peptides and their receptors suggests that they may each have unique paracrine functions within the testis.