Article

Kisspeptin Synchronizes Preovulatory Surges in Cyclical Ewes and Causes Ovulation in Seasonally Acyclic Ewes

University of Tours, Tours, Centre, France
Endocrinology (Impact Factor: 4.5). 12/2007; 148(11):5258-67. DOI: 10.1210/en.2007-0554
Source: PubMed

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.

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    • "The expression within the ventral posterior area (including the ARC) was greater than the expression within the anterior area (including the POA) (Ainu Husna et al., 2013). These interspecies variations in Kiss-1 distribution might be due to factors related to differences between seasonal/ non-seasonal animal species, sex steroid hormone effects, nutritional status, anatomical and physiological variations, and differences in the volume of kisspeptin synthesized from different hypothalamic nuclei (Caraty et al, 2007;Colledge, 2008;Overgaard et al., 2013;Poling and Kauffman, 2013;Liu et al., 2014;Cui et al., 2015). In addition to the finding of Kiss-1 mRNA in buffalo POA and ARC areas, the results of our study's immunohistochemistry testing found evidence of kisspeptin synthesized from Kiss-1 mRNA. "
    [Show abstract] [Hide abstract] ABSTRACT: In ruminants, the preoptic area (POA) and arcuate (ARC) are the main hypothalamic nuclei through which kisspeptin influences gonadotropin releasing hormone (GnRH) neurons for reproductive functions. The relationship between kisspeptin and GnRH releasing in many species has been studied, but not in buffalo. The aims of this study were to detect the localization of Kiss-1 mRNA and the distribution of kisspeptin protein in the POA and ARC hypothalamic nuclei of cycling buffalo cows. Brains were collected from 6 buffaloes and processed for paraffin blocks. Four-micron paraffin sections of the POA and ARC hypothalamic nuclei were prepared for (1) chromogenic in situ hybridization using a Kiss-1cRNA probe designed from the ovine kisspeptin gene sequence (GenBank accession no. DQ059506) and (2) immunohistochemistry using a rabbit anti-mouse kisspeptin-10 antibody. The signals for Kiss-1 mRNA and the localization of kisspeptin proteins were detected in the cytoplasm of the POA and ARC neuronal soma and some small neuronal cells. Kisspeptin proteins were also found in the cellular process of the POA and ARC neurons. The population of kisspeptin-immunoreactive neurons distributed in the POA (79.8 +/- 2.5%) was greater than in the ARC area (62.5 +/- 4.5%) (P <= 0.01). This study provides evidence of Kiss-1 mRNA and kisspeptin protein in the hypothalamus of buffalo, and it will hopefully help lay the groundwork for a further understanding of the role of kisspeptin in buffalo and its relation to reproduction and the hypothalamic-pituitary-gonadal axis. (c) 2015 PVJ. All rights reserved
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    • "This lack of effect might reflect a loss of responsiveness produced by continuous kisspeptin administration as seen in some other species (Ramaswamy et al., 2007), but this seems unlikely because intermittent administration (once/day) was also ineffective in Siberian hamsters (Greives et al., 2008b). It is interesting to note in this regard that constant infusion of kisspeptin was more effective than intermittent (twice/day) injection in inducing ovulation in anestrous ewes (Caraty et al., 2007), and that continuous icv administration of this peptide (6 nmoles/day) to Syrian hamsters exposed to short days stimulated testicular growth (). On the other hand, a similar dose of kisspeptin (10 nmoles/day) failed to stimulate testicular growth in Syrian hamsters when given sc (Ansel et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Seasonal reproduction is a common adaptive strategy among mammals that allows for breeding to occur at times of the year when it is most advantageous for the subsequent survival and growth of offspring. A major mechanism responsible for seasonal reproduction is a striking increase in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the negative feedback effects of estradiol. The neural and neuroendocrine circuitry responsible for mammalian seasonal reproduction has been primarily studied in three animal models: the sheep, and two species of hamsters. In this review, we first describe the afferent signals, neural circuitry and transmitters/peptides responsible for seasonal reproductive transitions in sheep, and then compare these mechanisms with those derived from studies in hamsters. The results suggest common principles as well as differences in the role of specific brain nuclei and neuropeptides, including that of kisspeptin cells of the hypothalamic arcuate nucleus, in regulating seasonal reproduction among mammals.
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    • "Intracerebroventricular perfusion of KP10 (0.25 nmol/h) for 4 wk in SDmaintained hamsters elicited a full reactivation of the reproductive axis as measured by the increase of testicular size and of testosterone-circulating levels (Revel et al., 2006 ). As mentioned above, in anoestrus ewe, an intravenous perfusion of low doses of KP10 for 48 h was able to induce ovulation in 80% of the animals (Caraty et al., 2007). Hence, in hamsters as in sheep, KP is a key factor for the reinstatement of the breeding season. "
    [Show abstract] [Hide abstract] ABSTRACT: Kisspeptin, an endogenous neuropeptide, is the most potent secretagogue of gonadotropin-releasing hormone. In seasonally breeding mammals, kisspeptin is strongly regulated by daylength (photoperiod), and seasonal anoestrus can be overcome by kisspeptin treatment. Kisspeptin is also suspected to be involved in metabolism regulation. Current investigations are trying to elucidate neuronatomical and functional relationships between hypothalamic populations controlling food intake and kisspeptin neurons. There is a clear interest in developing kisspeptin analogs to control reproduction in livestock and to treat reproduction-related human diseases. Current work is aiming at developing molecules with improved pharmacokinetics and pharmacodynamics.
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