Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes

Endocrinology. 2007 Nov;148(11):5258-67. doi: 10.1210/en.2007-0554. Epub 2007 Aug 16.

Abstract

We determined whether kisspeptin could be used to manipulate the gonadotropin axis and ovulation in sheep. First, a series of experiments was performed to determine the gonadotropic responses to different modes and doses of kisspeptin administration during the anestrous season using estradiol-treated ovariectomized ewes. We found that: 1) injections (iv) of doses as low as 6 nmol human C-terminal Kiss1 decapeptide elevate plasma LH and FSH levels, 2) murine C-terminal Kiss1 decapeptide was equipotent to human C-terminal Kiss1 decapeptide in terms of the release of LH or FSH, and 3) constant iv infusion of kisspeptin induced a sustained release of LH and FSH over a number of hours. During the breeding season and in progesterone-synchronized cyclical ewes, constant iv infusion of murine C-terminal Kiss1 decapeptide-10 (0.48 mumol/h over 8 h) was administered 30 h after withdrawal of a progesterone priming period, and surge responses in LH occurred within 2 h. Thus, the treatment synchronized preovulatory LH surges, whereas the surges in vehicle-infused controls were later and more widely dispersed. During the anestrous season, we conducted experiments to determine whether kisspeptin treatment could cause ovulation. Infusion (iv) of 12.4 nmol/h kisspeptin for either 30 or 48 h caused ovulation in more than 80% of kisspeptin-treated animals, whereas less than 20% of control animals ovulated. Our results indicate that systemic delivery of kisspeptin provides new strategies for the manipulation of the gonadotropin secretion and can cause ovulation in noncyclical females.

Publication types

  • Comparative Study
  • Evaluation Study
  • Multicenter Study

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Estrous Cycle / blood
  • Estrous Cycle / drug effects*
  • Female
  • Follicular Phase / blood
  • Follicular Phase / drug effects*
  • Gonadotropin-Releasing Hormone / cerebrospinal fluid
  • Gonadotropins / blood*
  • Humans
  • Kisspeptins
  • Mice
  • Oligopeptides / pharmacology*
  • Ovulation / blood
  • Ovulation / drug effects*
  • Ovulation Induction / methods
  • Ovulation Induction / veterinary
  • Reproduction / drug effects
  • Seasons
  • Sheep*

Substances

  • Gonadotropins
  • KISS1 protein, human
  • Kisspeptins
  • Oligopeptides
  • Gonadotropin-Releasing Hormone