The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin inhibit gonadotropin secretion via feedback from the gonads, but a neuropeptide inhibitor of gonadotropin secretion was, until recently, unknown in vertebrates. In 2000, we identified a novel hypothalamic dodecapeptide that inhibits gonadotropin release in cultured quail pituitaries and termed it gonadotropin-inhibitory hormone (GnIH). To elucidate the mode of action of GnIH, we then identified a novel G protein-coupled receptor for GnIH in quail. The GnIH receptor possesses seven transmembrane domains and specifically binds to GnIH. The GnIH receptor is 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 regulatory neuropeptide in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in quail. Chronic treatment with GnIH inhibited gonadal development and maintenance by decreasing gonadotropin synthesis and release. GnIH was also found in the hypothalamus of other avian species including sparrows and chickens and also inhibited gonadotropin synthesis and release. The pineal hormone melatonin may be a key factor controlling GnIH neural function, since quail GnIH neurons express melatonin receptor and melatonin treatment stimulates the expression of GnIH mRNA and mature GnIH peptide. Thus, GnIH is capable of transducing photoperiodic information via changes in the melatonin signal, thereby influencing the reproductive axis. It is concluded that GnIH, a newly discovered hypothalamic neuropeptide, is a key factor controlling avian reproduction. The discovery of avian GnIH opens a new research field in reproductive neuroendocrinology.
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