Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis.
Kisspeptin is the peptide product of the KiSS-1 gene and the endogenous agonist for the GPR54 receptor. Recent evidence suggests the kisspeptin/GPR54 system is a key regulator of the reproductive system. We examined the effect of intracerebroventricular (i.c.v.) and peripheral administration of the active kisspeptin fragment, kisspeptin-10, on circulating gonadotrophins and total testosterone levels in adult male rats. The effect of kisspeptin-10 in vitro on the release of hypothalamic peptides from hypothalamic explants and gonadotrophins from anterior pituitary fragments was also determined. The i.c.v. administration of kisspeptin-10 dose-dependently increased plasma luteinizing hormone (LH) and increased plasma follicle stimulating hormone (FSH) and total testosterone at 60 min postinjection. In a separate study investigating the time course of this response, i.c.v. administered kisspeptin-10 (3 nmol) significantly increased plasma LH at 10, 20 and 60 min, FSH at 60 min and total testosterone at 20 and 60 min postinjection. Kisspeptin-10 stimulated the release of luteinizing hormone-releasing hormone (LHRH) from in vitro hypothalamic explants. Peripheral administration of kisspeptin-10 increased plasma LH, FSH and total testosterone. However, doses of 100-1000 nM kisspeptin-10 did not influence LH or FSH release from pituitary fragments in vitro. Kisspeptin therefore potently stimulates the hypothalamic-pituitary-gonadal axis. These effects are likely to be mediated via the hypothalamic LHRH system.
Thompson
E L
EL
Department of Metabolic Medicine, Imperial College Faculty of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Patterson
M
M
Murphy
K G
KG
Smith
K L
KL
Dhillo
W S
WS
Todd
J F
JF
Ghatei
M A
MA
Bloom
S R
SR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000523:psychology; D006062:Gonadotropins / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007276:Injections, Intraventricular; D059648:Kisspeptins; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D010907:Pituitary Hormones / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000378:metabolism
D006062:Gonadotropins; C106628:KISS1 protein, human; D059648:Kisspeptins; D009842:Oligopeptides; D010907:Pituitary Hormones; D013739:Testosterone