Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis.
The hypothalamus plays a key role in the regulation of both energy homeostasis and reproduction. Evidence suggests that relaxin-3, a recently discovered member of the insulin superfamily, is an orexigenic hypothalamic neuropeptide. Relaxin-3 is thought to act in the brain via the RXFP3 receptor, although the RXFP1 receptor may also play a role. Relaxin-3, RXFP3, and RXFP1 are present in the hypothalamic paraventricular nucleus, an area with a well-characterized role in the regulation of energy balance that also modulates reproductive function by providing inputs to hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Other members of the relaxin family are known to play a role in the regulation of reproduction. However, the effects of relaxin-3 on reproductive function are unknown. We studied the role of relaxin-3 in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. Intracerebroventricular (5 nmol) and intraparaventricular (540-1,620 pmol) administration of human relaxin-3 (H3) in adult male Wistar rats significantly increased plasma luteinizing hormone (LH) 30 min postinjection. This effect was blocked by pretreatment with a peripheral GnRH antagonist. Central administration of human relaxin-2 showed no significant effect on plasma LH. H3 dose-dependently stimulated the release of GnRH from hypothalamic explants and GT(1)-7 cells, which express RXFP1 and RXFP3, but did not influence LH or follicle-stimulating hormone release from pituitary fragments in vitro. We have demonstrated a novel role for relaxin-3 in the stimulation of the HPG axis, putatively via hypothalamic GnRH neurons. Relaxin-3 may act as a central signal linking nutritional status and reproductive function.
McGowan
B M
BM
Dept. of Investigative Medicine, Division of Investigative Science, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK.
Stanley
S A
SA
Donovan
J
J
Thompson
E L
EL
Patterson
M
M
Semjonous
N M
NM
Gardiner
J V
JV
Murphy
K G
KG
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D002460:Cell Line; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics; D012065:Relaxin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000378:metabolism
D006727:Hormone Antagonists; C480238:RLN3 protein, human; D043562:Receptors, G-Protein-Coupled; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D012065:Relaxin; C062876:cetrorelix