EXON SKIPPING IN THE GENE ENCODING PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE IN SALMON ALTERS THE EXPRESSION OF 2 HORMONES THAT STIMULATE GROWTH-HORMONE RELEASE

In mammals, GRF and pituitary adenylate cyclase-activating polypeptide (PACAP) are encoded in separate genes. We report here that in the sal mon a 4.5-kilobase gene contains live exons that encode the biological ly active part of the GRF-like peptide (amino acids 1-32) on exon 4 an d PACAP on exon 5. Analysis of two fish messenger RNAs reveals that a long precursor containing GRF and PACAP and a short precursor containi ng only PACAP are both expressed in the blain of at least five species of salmon, whereas mice express only the long precursor encoded by th e PACAP gene. Synthetic salmon PACAP-38 and salmon GRF-like peptide-45 both stimulated GH release from cultured salmon pituitary cells; PACA P stimulated a concentration-dependent release of GH ab both 4 and 24 h of incubation, whereas GRF-like peptide did not. Alternative splicin g, resulting in the short precursor in which GRF-32 is excised, may pr ovide a means for differential control of GH secretion with higher pro duction of the more potent PACAP. A duplication of the GRF-like/PACAP gene in evolution after the divergence of fish and tetrapods would exp lain separate genes and regulation for GRF and PACAP in mammals.