title: LPXRFa, the piscine ortholog of GnIH, and LPXRF receptor positively regulate gonadotropin secretion in Tilapia (Oreochromis niloticus).
abstract: LPXRFamide (LPXRFa) peptides have been characterized for their ability to inhibit gonadotropin (GTH) release in birds and stimulate growth hormone (GH) release in frogs. However, their involvement in regulating the reproductive hypothalamo-pituitary-gonadal axis in mammals and fish is inconclusive. To study the role of LPXRFa peptides in the regulation of GTH secretion, we cloned tilapia LPXRFa and LPXRF receptor (LPXRF-R). Processing of the tilapia preproLPXRFa liberated three mature LPXRFa peptides that varied in size and post-translational modifications. Phylogenetic analysis of LPXRFa and the closely related RFamide peptide PQRFa showed clear clustering of each peptide sequence with its orthologs from various vertebrates. Signal-transduction analysis of the tilapia LPXRF-R in COS-7 cells showed clear stimulation of CRE-dependent luciferase activity, whereas the human NPFFR1 showed suppression of forskolin-induced CRE-dependent activity in this system. Administration of the tilapia pyroglutaminated LPXRFa-2 peptide to primary cell culture of tilapia pituitaries, or to reproductive female tilapia by ip injection, positively regulated both LH and FSH release in vivo and in vitro. Using double-labeled fluorescent in-situ hybridization and immunofluorescence, βLH cells were found to co-express both tilapia lpxrf and tilapia lpxrf-r mRNA, whereas some of the βFSH cells coexpressed only lpxrf-r mRNA. No coexpression of tilapia lpxrf-r was identified in GH-positive cells. These findings suggest that the LPXRFa system is a potent positive regulator of the reproductive neuroendocrine axis of tilapia.
authors.affiliation: Department of Animal Sciences (J.B., M.G., N.M., B.L.S.), The Robert H. Smith Faculty of Agriculture, Food, and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel; and Brain Research Institute (S.O., I.S.P.), Monash University, Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, Selangor 46150, Malaysia.
authors.forename: Jakob
authors.initials: J
authors.lastname: Biran
authors.forename: Matan
authors.initials: M
authors.lastname: Golan
authors.forename: Naama
authors.initials: N
authors.lastname: Mizrahi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Ishwar S
authors.initials: IS
authors.lastname: Parhar
authors.forename: Berta
authors.initials: B
authors.lastname: Levavi-Sivan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D023681:Cichlids / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D005260:Female; D006062:Gonadotropins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D010802:Phylogeny; D018013:Receptors, Neuropeptide / Q000502:physiology*; D017385:Sequence Homology
chemical_list: D006062:Gonadotropins; D009479:Neuropeptides; C416987:RFamide peptide; D018013:Receptors, Neuropeptide; C083929:neuropeptide FF receptor