Evolution of a Neuropeptide Family: Gonadotropin-Releasing Hormone

SYNOPSIS. Gonadotropin-releasing hormone (GnRH), a small peptidein the brain, is essential for reproduction. It is now clearthat GnRH is part of a family of closely related molecules.The primary structure has been identified for 4 GnRH molecules:mammalian, chicken I, chicken II and salmon. During evolutionthe molecule has been conserved in length, terminal amino acidstructure, 70–90% of amino acid sequence and the His²Trp³residues,residues, which are important in the release of gonadotropin.Alterations have occurred in positions 5, 7 and 8, regions thoughtto be involved in receptor binding. The receptors for GnRH haveapparently evolved also in that the mammalian and avian receptorsvary considerably in their ability to bind different GnRH molecules.Other GnRH family members have been distinguished indirectlyby chromatographic or immunological means; 3 different GnRH-likemolecules are present, respectively, in lamprey, sturgeon andsalmon (a second form). Several GnRH-like molecules includingthose in chondrichthyes have not yet been distinguished fromthe proposed salmon II molecule. The lamprey GnRH-like moleculemay be a nodal point inthe analysis of the ancestral molecule;hagfish do not contain a detectable GnRH molecule. The elucidationof the GnRH precursor molecule in human placenta showed thepresence of a 53-amino-acid gene-related peptide of unknownfunction, but did not reveal the basis for expression of multipleGnRH forms in many nonmammalian species. GnRH has a varietyof novel functions in addition to release of gonadotropin fromthe pituitary. During evolution certain functions such as thosein the retina and sympathetic ganglia have apparently disappearedin amniotes, but GnRH placental functions have appeared in mammals.