title: Discovery of growth hormone-releasing hormones and receptors in nonmammalian vertebrates.
abstract: In mammals, growth hormone-releasing hormone (GHRH) is the most important neuroendocrine factor that stimulates the release of growth hormone (GH) from the anterior pituitary. In nonmammalian vertebrates, however, the previously named GHRH-like peptides were unable to demonstrate robust GH-releasing activities. In this article, 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 receptors (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 neighboring genes confirmed that they share the same origins as the mammalian genes. Functionally, the goldfish GHRH dose-dependently activates cAMP production in receptor-transfected CHO cells as well as GH release from goldfish pituitary cells. Tissue distribution studies showed that the goldfish GHRH is expressed almost exclusively in the brain, whereas the goldfish GHRH-R is actively expressed in brain and pituitary. Taken together, these results provide evidence for a previously uncharacterized GHRH-GHRH-R axis in nonmammalian vertebrates. Based on these data, a comprehensive evolutionary scheme for GHRH, PRP-PACAP, and PHI-VIP genes in relation to three rounds of genome duplication early on in vertebrate evolution is proposed. These GHRHs, also found in flounder, Fugu, medaka, stickleback, Tetraodon, and rainbow trout, provide research directions regarding the neuroendocrine control of growth in vertebrates.
authors.affiliation: Department of Zoology, University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors.forename: Leo T O
authors.initials: LT
authors.lastname: Lee
authors.forename: Francis K Y
authors.initials: FK
authors.lastname: Siu
authors.forename: Janice K V
authors.initials: JK
authors.lastname: Tam
authors.forename: Ivy T Y
authors.initials: IT
authors.lastname: Lau
authors.forename: Anderson O L
authors.initials: AO
authors.lastname: Wong
authors.forename: Marie C M
authors.initials: MC
authors.lastname: Lin
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Billy K C
authors.initials: BK
authors.lastname: Chow
mesh_terms: D000818:Animals; D001001:Anura; D000242:Cyclic AMP / Q000096:biosynthesis; D019143:Evolution, Molecular; D006054:Goldfish; D013007:Growth Hormone-Releasing Hormone / Q000032:analysis / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018013:Receptors, Neuropeptide / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution; D014714:Vertebrates; D015027:Zebrafish
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C099166:growth hormone releasing hormone-related peptide; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP; C048250:somatotropin releasing hormone receptor