Kisspeptin, a new key player in reproduction control

The discovery of the role of kisspeptin and of its cognate receptor, KISS1R, has been a breakthrough in the understanding of the mechanisms underpinning reproduction and in particular GnRH secretion. The injection of kisspeptin in various mammalian species showed its capacity to stimulate GnRH secretion and to trigger ovulation in anoestrus ewe. This capacity is under the control of sexual hormones that act directly and with opposite effects on the two kisspeptin neuronal populations present in the hypothalamus. There is a clear interest for the use of this molecule in farming and in human medicine although its short half-life has until now hampered its exploitation. The design of analogs with longer half-life represents a possible solution and preliminary results look promisingLa découverte de la kisspeptine et de son récepteur, KISS1R, a permis une avancée majeure dans la compréhension des mécanismes qui contrôlent la reproduction et plus particulièrement, la sécrétion de la GnRH. L’administration de la kisspeptine chez différentes espèces de mammifères permet de stimuler la sécrétion de la GnRH et chez la brebis, d’induire l’ovulation en contre-saison. Son action sur la libération de la GnRH est sous le rétrocontrôle à la fois positif et négatif des hormones sexuelles qui agissent directement et de façon opposée sur les deux populations de neurones à kisspeptine présentes dans l’hypothalamus. L’intérêt de cette molécule pour une utilisation en élevage ou en clinique humaine est évident, mais sa demi-vie très courte a été pour le moment un frein à son exploitation. La création d’analogues à durée d’action accrue représente une solution possible à ce problème et les premiers résultats sont encourageant

Neuroanatomical organization of gonadotropin-releasing hormone neurons during the oestrus cycle in the ewe

BACKGROUND: During the preovulatory surge of gonadotropin-releasing hormone (GnRH), a very large amount of the peptide is released in the hypothalamo-hypophyseal portal blood for 24-36H00. To study whether this release is linked to a modification of the morphological organization of the GnRH-containing neurons, i.e. morphological plasticity, we conducted experiments in intact ewes at 4 different times of the oestrous cycle (before the expected LH surge, during the LH surge, and on day 8 and day 15 of the subsequent luteal phase). The cycle stage was verified by determination of progesterone and LH concentrations in the peripheral blood samples collected prior to euthanasia. RESULTS: The distribution of GnRH-containing neurons throughout the preoptic area around the vascular organ of the lamina terminalis was studied following visualisation using immunohistochemistry. No difference was observed in the staining intensity for GnRH between the different groups. Clusters of GnRH-containing neurons (defined as 2 or more neurons being observed in close contact) were more numerous during the late follicular phase (43 ± 7) than during the luteal phase (25 ± 6), and the percentage of clusters was higher during the beginning of the follicular phase than during the luteal phase. There was no difference in the number of labelled neurons in each group. CONCLUSIONS: These results indicate that the morphological organization of the GnRH-containing neurons in ewes is modified during the follicular phase. This transitory re-organization may contribute to the putative synchronization of these neurons during the surge. The molecular signal inducing this plasticity has not yet been identified, but oestradiol might play an important role, since in sheep it is the only signal which initiates the GnRH preovulatory surge

Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration

Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading causes of infertility in women aged 25-34. Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused female mice with prolactin. Our studies demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists

Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration

Hyperprolactinemia is the most common cause of hypogonadotropic anovulation and is one of the leading causes of infertility in women aged 25–34. Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. To mimic the human pathology of anovulation, we continuously infused female mice with prolactin. Our studies demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation. Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists.R. Millar is recipient of a grant from the Medical Research Council (South Africa) and the University of Pretoria.http://www.jci.or

Contribution a l'etude des mecanismes de retroaction testiculaire : controle de la secretion et du mode d'action de la LH-RH

SIGLET 55286 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Le contrôle central de l'ovulation à travers les âges!!! Que nous a apporté le modèle mouton à sa compréhension?

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Le système kisspeptine/GPR54 : la clé majeure du contrôle de la reproduction

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Stimulation of the gonadotropin axis by kisspeptin: potential application to manipulate reproduction in domestic animals

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Contribution de la neurochirurgie à l'étude de la libération de GnRH chez la brebis

National audienceThis article describes the main surgical approaches used in sheep to measure the release of GnRH, the hypothalamic hormone controlling the reproductive function. Two methods have been developed in this species: the hypophyseal portal blood collection and the sampling of cerebrospinal fluid from the third ventricle of the brain. These methods have demonstrated that GnRH is secreted during very short periods of time, called pulses. The GnRH pulses are the link between the neuronal signal and the hormonal signal. The brain controls the stages of the reproductive life through the variation of GnRH pulse frequency. Just prior to ovulation, GnRH secretion is no longer strictly pulsatile and forms a surge, which induces a peak in LH, which in turns triggers ovulation. The GnRH surge extends well beyond that of the preovulatory LH surge

Measurement and possible function of GnRH in cerebrospinal fluid in ewes

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