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


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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    • "GnRH injection during KP10 perfusion resulted in LH secretion stimulation, suggesting that KP10 perfusion was desensitizing KISS1R rather than depleting GnRH or LH stores (Seminara et al., 2006). On the other hand, a continuous KP perfusion at 12.6 nmoles/h stimulated ovulation in anoestrus ewes (Caraty et al., 2007). These conflicting results suggest that the dose and the regimen of KP administration are of prime importance in succeeding or not to obtain a prolonged LH secretion and consequently important for zootechnical and therapeutic applications. "
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    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.
    Full-text · Article · Jan 2015
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    • "Across species, kisspeptin is generally elevated during the breeding season and suppressed following exposure to inhibitory photoperiods or appropriately timed melatonin administration . Likewise, infusion of kisspeptin can restore reproductive function to reproductively quiescent hamsters and sheep (Ansel et al., 2011; Caraty et al., 2007). Together with the aforementioned overview of the participation of GnIH in mammalian seasonality, these findings point to an important role for kisspeptin in the regulation of seasonal breeding. "
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    ABSTRACT: Animals inhabiting temperate and boreal latitudes experience marked seasonal changes in the quality of their environments and maximize reproductive success by phasing breeding activities with the most favorable time of year. Whereas the specific mechanisms driving seasonal changes in reproductive function vary across species, converging lines of evidence suggest gonadotropin-inhibitory hormone (GnIH) serves as a key component of the neuroendocrine circuitry driving seasonal changes in reproduction and sexual motivation in some species. In addition to anticipating environmental change through transduction of photoperiodic information and modifying reproductive state accordingly, GnIH is also positioned to regulate acute changes in reproductive status should unpredictable conditions manifest throughout the year. The present overview summarizes the role of GnIH in avian and mammalian seasonal breeding while considering the similarities and disparities that have emerged from broad investigations across reproductively photoperiodic species. Copyright © 2014. Published by Elsevier Inc.
    Full-text · Article · Dec 2014 · Frontiers in Neuroendocrinology
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    • "There is also evidence that kisspeptin acts at the level of the GnRH neuron dendrites within the organum vasculosum of the lamina terminalis (OVLT) to activate GnRH neuron firing (Herde et al., 2011). These sites of kisspeptin activation of GnRH neurons within the MBH and OVLT are outside the blood–brain-barrier and may underlie the ability of peripheral administration of kisspeptin to activate luteinizing hormone (LH) secretion in mammals (Caraty et al., 2007; Dhillo et al., 2005; Messager et al., 2005; Shahab et al., 2005; Thompson et al., 2004; Tovar et al., 2006). "
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    ABSTRACT: Kisspeptin neurons are critical components of the neuronal network controlling the activity of the gonadotropin-releasing hormone (GnRH) neurons. A variety of genetically-manipulated mouse models have recently facilitated the study of the electrical activity of the two principal kisspeptin neuron populations located in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (ARN) in acute brain slices. We discuss here the mechanisms and pathways through which kisspeptin neurons regulate GnRH neuron activity. We then examine the different kisspeptin-green fluorescent protein mouse models being used for kisspeptin electrophysiology and the data obtained to date for RP3V and ARN kisspeptin neurons. In light of these new observations on the spontaneous firing rates, intrinsic membrane properties, and neurotransmitter regulation of kisspeptin neurons, we speculate on the physiological roles of the different kisspeptin populations.
    Full-text · Article · Jun 2014 · Frontiers in Neuroendocrinology
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