Gonadotropin-Inhibitory Hormone (GnIH): Discovery, Progress and Perspective

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  • Tsutsui Kazuyoshi
    Laboratory of Brain Science, Faculty of Integrated Arts and Sciences, Hiroshima University, and Integrative Brain Science Center at Hiroshima University

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Abstract

Probing undiscovered neuropeptides that play important roles in the regulation of pituitary function is essential for the progress of avian endocrinology and neuroendocrinology. Neuropeptide control of gonadotropin secretion at the level of the anterior pituitary gland is primarily through the stimulatory action of the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH). Until recently, any neuropeptide that directly inhibits gonadotropin secretion has not been identified. In 2000, we discovered a novel hypothalamic dodecapeptide that directly inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). A gonadotropin inhibitory system is an intriguing concept and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To elucidate the mode of action of GnIH, we have identified a novel G protein-coupled receptor for GnIH in quail. The GnIH receptor possessed seven transmembrane domains and specifically bound to GnIH. The GnIH receptor was found to be expressed in the pituitary and several brain regions including the hypothalamus. These results indicate that GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin release. GnIH may also act on the hypothalamus to inhibit GnRH release. To demonstrate the functional significance of GnIH and its potential role as a key neuropeptide involved in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in quail. Chronic treatment with GnIH inhibited gonadal development and maintenance by the decreasing gonadotropin synthesis and release. Melatonin is a key factor for involved in GnIH neural function, because quail GnIH neurons contain melatonin receptor and melatonin treatment stimulates expression of GnIH mRNA and mature GnIH peptide. Thus GnIH is capable of transducing photoperiodic information via changes in the melatonin signal and to influence the reproductive axis of birds. It is concluded that GnIH, a newly discovered hypothalamic neuropeptide, acts as an important factor on avian reproduction.

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