Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis

J Neuroendocrinol. 2004 Oct;16(10):850-8. doi: 10.1111/j.1365-2826.2004.01240.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Circadian Rhythm / physiology
  • Dose-Response Relationship, Drug
  • Eating / drug effects
  • Fasting / psychology
  • Gonadotropins / metabolism
  • Hypothalamo-Hypophyseal System / drug effects*
  • Injections, Intraventricular
  • Kisspeptins
  • Male
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacology*
  • Pituitary Gland, Anterior / metabolism
  • Pituitary Hormones / blood
  • Rats
  • Rats, Wistar
  • Stimulation, Chemical
  • Testis / drug effects*
  • Testosterone / metabolism


  • Gonadotropins
  • KISS1 protein, human
  • Kisspeptins
  • Oligopeptides
  • Pituitary Hormones
  • Testosterone