title: Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion.
abstract: We identified a gene in the ovine hypothalamus encoding for RFamide-related peptide-3 (RFRP-3), and tested the hypothesis that this system produces a hypophysiotropic hormone that inhibits the function of pituitary gonadotropes. The RFRP-3 gene encodes for a peptide that appears identical to human RFRP-3 homolog. Using an antiserum raised against RFRP-3, cells were localized to the dorsomedial hypothalamic nucleus/paraventricular nucleus of the ovine brain and shown to project to the neurosecretory zone of the ovine median eminence, predicating a role for this peptide in the regulation of anterior pituitary gland function. Ovine RFRP-3 peptide was tested for biological activity in vitro and in vivo, and was shown to reduce LH and FSH secretion in a specific manner. RFRP-3 potently inhibited GnRH-stimulated mobilization of intracellular calcium in gonadotropes. These data indicate that RFRP-3 is a specific and potent mammalian gonadotropin-inhibiting hormone, and that it acts upon pituitary gonadotropes to reduce GnRH-stimulated gonadotropin secretion.
authors.affiliation: Department Physiology, Building 13F, Monash University, Clayton Victoria 3800, Australia. iain.clarke@med.monash.edu.au
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Clarke
authors.forename: Ika P
authors.initials: IP
authors.lastname: Sari
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Smith
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ubuka
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Alan
authors.initials: A
authors.lastname: Tilbrook
authors.forename: Kevin
authors.initials: K
authors.lastname: Morgan
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Pawson
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Tsutsui
authors.forename: Robert P
authors.initials: RP
authors.lastname: Millar
authors.forename: George E
authors.initials: GE
authors.lastname: Bentley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D052681:Gonadotrophs / Q000187:drug effects / Q000378:metabolism*; D006062:Gonadotropins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D010906:Pituitary Hormone-Releasing Hormones / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012756:Sheep / Q000235:genetics* / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D006062:Gonadotropins; D009479:Neuropeptides; D010906:Pituitary Hormone-Releasing Hormones; C416987:RFamide peptide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002118:Calcium