We determined whether kisspeptin could be used to manipulate the gonadotropin axis and ovulation in sheep. Firstly, 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 of human C-terminal Kiss1 decapeptide (hKp10) elevate plasma LH and FSH levels, 2) Murine C-terminal Kiss1 decapeptide (mKp10) was equipotent to hKp10 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 cyclic ewes, constant iv infusion of mKp10 (0.48 micromol/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, while less than 20 of control animals ovulated. Our results indicate that systemic delivery of kisspeptin provide new strategies for the manipulation of the gonadotropin secretion and can cause ovulation in non-cyclic females.
|Pages (from-to)||5258 - 5267|
|Number of pages||10|
|Publication status||Published - 2007|