Laboratory of Animal Production Science

Laboratory of Animal Production Science, Nagoya University

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OHKURA, Satoshi

Neuroendocrine mechanisms regulating pulsatile GnRH release in ruminants

Livestock products, such as meat and milk, are important food resources for human beings. From the standpoint of protecting the global environment, it is necessary to breed livestock efficiently using limited material resources, land and human resources, etc., effectively. If the minimum number of domestic animals required for food supply is maintained by efficient livestock breeding, a sustainable animal husbandry can be achieved. In recent years, the reproductive efficiency of livestock animals continues to decline not only in Japan but worldwide, and it has become an urgent issue to be solved in livestock industry. To improve the reproductive performance in livestock, it is necessary to develop a better understanding of the physiological mechanism that controls reproduction in domestic animals.

Reproductive processes in female mammals, such as follicular development in the ovary, ovulation of dominant follicles, and sexual and maternal behaviors, etc., are under control of the brain. The release of gonadotropin-releasing hormone (GnRH) from the hypothalamus is the top of neuroendocrine control hierarchy of ovarian activity and estrus cycles. Two modes of GnRH release are well recognized to regulate the estrous cycle. One is the tonic or pulse mode of secretion, which is primarily responsible for the follicular development and steroidogenesis. The other is the surge mode of secretion, which is solely responsible for the induction of GnRH/luteinizing hormone (LH) surges, which induce ovulation. The pattern of pulsatile GnRH release is a key determinant regulating the gonadal activity. The pulsatile secretion of GnRH is associated with synchronized electrical activity in the mediobasal hypothalamus (multiple unit activity; MUA), which is thought to reflect the rhythmic oscillations in the activity of the neuronal network, the GnRH pulse generator, which drives pulsatile GnRH secretion. However, the cellular source of this ultradian rhythm in GnRH release has not been fully elucidated.

Kisspeptin (firstly named metastin) is a peptide encoded by the metastasis suppressor gene, Kiss1. Growing evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC) play pivotal roles in the control of GnRH release. Our recent finding suggests that, in goats, the kisspeptin neurons in the ARC may be the intrinsic source of the GnRH pulse generator using multiple unit activity (MUA) recording technique (J. Neuroendocrinol. 21:813-821, 2009). In the series of studies in goats, we proposed a model for the generation of rhythmic oscillation of activity in kisspeptin neurons in the ARC and the pulsatile release of GnRH.