Potent action of RFamide-related peptide-3 on pituitary gonadotropes indicative of a hypophysiotropic role in the negative regulation of gonadotropin secretion.
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.
Clarke
Iain J
IJ
Department Physiology, Building 13F, Monash University, Clayton Victoria 3800, Australia. iain.clarke@med.monash.edu.au
Sari
Ika P
IP
Qi
Yue
Y
Smith
Jeremy T
JT
Parkington
Helena C
HC
Ubuka
Takayoshi
T
Iqbal
Javed
J
Li
Qun
Q
Tilbrook
Alan
A
Morgan
Kevin
K
Pawson
Adam J
AJ
Tsutsui
Kazuyoshi
K
Millar
Robert P
RP
Bentley
George E
GE
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
D018076:DNA, Complementary; D006062:Gonadotropins; D009479:Neuropeptides; D010906:Pituitary Hormone-Releasing Hormones; C416987:RFamide peptide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002118:Calcium