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Submitted on May 2, 2007
Accepted on August 6, 2007
UMR 6175, Physiologie de la Reproduction et des Comportements (INRA/CNRS/Université Tours/Haras Nationaux), 37380 Nouzilly, France; Dept Physiology, Monash University, Clayton, VIC 3800, Australia
* To whom correspondence should be addressed. E-mail: caraty{at}tours.inra.fr.
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 µmol/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.
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