Evolution of gonadotropin-inhibitory hormone receptor and its ligand.

Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide inhibitor of gonadotropin secretion, which was first identified in the Japanese quail hypothalamus. GnIH peptides share a C-terminal LPXRFamide (X=L or Q) motif in most vertebrates. The receptor for GnIH (GnIHR) is the seven-transmembrane G protein-coupled receptor 147 (GPR147) that inhibits cAMP production. GPR147 is also named neuropeptide FF (NPFF) receptor 1 (NPFFR1), because it also binds NPFF that has a C-terminal PQRFamide motif. To understand the evolutionary history of the GnIH system in the animal kingdom, we searched for receptors structurally similar to GnIHR in the genome of six mammals (human, mouse, rat, cattle, cat, and rabbit), five birds (pigeon, chicken, turkey, budgerigar, and zebra finch), one reptile (green anole), one amphibian (Western clawed flog), six fishes (zebrafish, Nile tilapia, Fugu, coelacanth, spotted gar, and lamprey), one hemichordate (acorn worm), one echinoderm (purple sea urchin), one mollusk (California sea hare), seven insects (pea aphid, African malaria mosquito, honey bee, buff-tailed bumblebee, fruit fly, jewel wasp, and red flour beetle), one cnidarian (hydra), and constructed phylogenetic trees by neighbor joining (NJ) and maximum likelihood (ML) methods. A multiple sequence alignment of the receptors showed highly conserved seven-transmembrane domains as well as disulfide bridge sites between the first and second extracellular loops, including the receptor of hydra. Both NJ and ML analyses grouped the receptors of vertebrates into NPFFR1 and NPFFR2 (GPR74), and the receptors of insects into the receptor for SIFamide peptides that share a C-terminal YRKPPFNGSIFamide motif. Although human, quail and zebrafish GnIHR (NPFFR1) were most structurally similar to SIFamide receptor of fruit fly in the Famide peptide (FMRFamide, neuropeptide F, short neuropeptide F, drosulfakinin, myosuppressin, SIFamide) receptor families, the amino acid sequences and the peptide coding regions of GnIH precursors were most similar to FMRFamide precursor of fruit fly in the precursors of Famide peptide families. Chromosome synteny analysis of the precursor genes of human, quail and zebrafish GnIH and fruit fly Famide peptides further identified conserved synteny in vertebrate GnIH and fruit fly FMRFa precursor genes as well as other Famide peptide precursor genes. These results suggest that GnIH and its receptor pair and SIFamide and its receptor pair may have diverged and co-evolved independently in vertebrates and insects, respectively, from their ancestral Famide peptide and its receptor pair, during diversification and evolution of deuterostomian and protostomian species.

Effects of human pancreatic growth hormone-releasing hormone and fragments of rat hypothalamic growth hormone-releasing hormone on the activity of rat brain neurons.

The effect of human pancreatic growth hormone-releasing factor (hpGRF), rat hypothalamic GRF1-29 (rhGRF1-29) and rhGRF3-40 on spontaneous extracellular activity was studied in urethane anesthetized, male rats. The results show that these peptides similarly depress the firing rate of responsive neurons in the amygdala, caudate-putamen and globus pallidus. A single neuron was excited by hpGRF and it was localized to the medial amygdala. These findings are in line with the hypothesis that GRF has effects on the central nervous system in addition to regulating pituitary growth hormone secretion.