Evolution of a Neuropeptide Family: Gonadotropin-Releasing Hormone

Abstract

SYNOPSIS. Gonadotropin-releasing hormone (GnRH), a small peptide in the brain, is essential for reproduction. It is now clear that 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 evolution the molecule has been conserved in length, terminal amino acid structure, 70–90% of amino acid sequence and the His2Trp3 residues,residues, which are important in the release of gonadotropin. Alterations have occurred in positions 5, 7 and 8, regions thought to be involved in receptor binding. The receptors for GnRH have apparently evolved also in that the mammalian and avian receptors vary considerably in their ability to bind different GnRH molecules. Other GnRH family members have been distinguished indirectly by chromatographic or immunological means; 3 different GnRH-like molecules are present, respectively, in lamprey, sturgeon and salmon (a second form). Several GnRH-like molecules including those in chondrichthyes have not yet been distinguished from the proposed salmon II molecule. The lamprey GnRH-like molecule may be a nodal point inthe analysis of the ancestral molecule; hagfish do not contain a detectable GnRH molecule. The elucidation of the GnRH precursor molecule in human placenta showed the presence of a 53-amino-acid gene-related peptide of unknown function, but did not reveal the basis for expression of multiple GnRH forms in many nonmammalian species. GnRH has a variety of novel functions in addition to release of gonadotropin from the pituitary. During evolution certain functions such as those in the retina and sympathetic ganglia have apparently disappeared in amniotes, but GnRH placental functions have appeared in mammals.