Endocrine Abstracts

In mammals, GHRH is the most important neuroendocrine factor that stimulates the release of GH from the anterior pituitary. In non-mammalian vertebrates, however, the previously named GHRH-like peptides were unable to demonstrate robust GH-releasing activities. In this report, we provide evidence that these GHRH-like peptides are homologues of mammalian PACAP-related peptides (PRP). Instead, GHRH peptides encoded in cDNAs isolated from goldfish, zebrafish and African clawed frog were identified. Moreover, receptors specific for these GHRHs were characterized from goldfish and zebrafish. These GHRHs and GHRH-Rs are phylogenetically and structurally more similar to their mammalian counterparts than the previously named GHRH-like peptides and GHRH-like receptors. Information regarding their chromosomal locations and organization of neighbouring genes confirmed also that they share the same origins as the mammalian genes. Functionally, the goldfish GHRH activates cAMP production in receptor-transfected CHO cells as well as GH release from goldfish pituitary cells. Tissue distribution studies by real-time PCR showed that the goldfish GHRH is expressed almost exclusively in the brain, while the goldfish GHRH-R is actively expressed in brain and pituitary. In addition, specific receptors for PRPs (formerly GHRH-like peptides) were cloned from goldfish, zebrafish and Xenopus, clearly suggesting a function of PRP in these species. By phylogenetic and chromosomal syntenic studies, we found PRP receptors only in non-mammalian vertebrates but not in mammals, indicating that the receptor was lost in the mammalian lineage. Based on these data, a comprehensive evolutionary scheme for GHRH, PRP-PACAP, PHI-VIP genes in relation to 3 rounds of genome duplication early on in vertebrate evolution is proposed. Finally, the newly discovered GHRHs, also found in flounder, Fugu, medaka, stickleback, Tetraodon and rainbow trout, provide new research directions regarding the neuroendocrine control of growth in vertebrates.