Exon skipping in the gene encoding pituitary adenylate cyclase-activating polypeptide in salmon alters the expression of two 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 salmon a 4.5-kilobase gene contains five exons that encode the biologically active part of the GRF-like peptide (amino acids 1-32) on exon 4 and PACAP on exon 5. Analysis of two fish messenger RNAs reveals that a long precursor containing GRF and PACAP and a short precursor containing only PACAP are both expressed in the brain of at least five species of salmon, whereas mice express only the long precursor encoded by the PACAP gene. Synthetic salmon PACAP-38 and salmon GRF-like peptide-45 both stimulated GH release from cultured salmon pituitary cells; PACAP stimulated a concentration-dependent release of GH at both 4 and 24 h of incubation, whereas GRF-like peptide did not. Alternative splicing, resulting in the short precursor in which GRF-32 is excised, may provide a means for differential control of GH secretion with higher production of the more potent PACAP. A duplication of the GRF-like/PACAP gene in evolution after the divergence of fish and tetrapods would explain separate genes and regulation for GRF and PACAP in mammals.