Discovery of gonadotropin-inhibitory hormone in a domesticated bird, its mode of action and functional significance

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) in vertebrates. Until recently, no neuropeptide that directly inhibits gonadotropin secretion had 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 then identified a novel G protein-coupled receptor for GnIH in quail. The receptor possessed seven transmembrane domains and specifically bound to GnIH in a concentration-dependent manner. 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, because GnIH fibers were observed to contact GnRH cell bodies. To demonstrate the functional significance of GnIH and its potential role as a key neuropeptide involved in avian reproduction, we further investigated the action of GnIH on gonadal development and maintenance in quail. Chronic treatment with GnIH inhibited photoinduced testicular development and maintenance by decreasing gonadotropin synthesis and release. Melatonin is a key factor involved in GnIH neural function. Quail GnIH neurons were found to contain melatonin receptor and melatonin stimulated expression of GnIH mRNA and mature GnIH peptide in a dose-dependent manner. It is concluded that GnIH is capable of transducing photoperiodic information via changes in the melatonin signal and of influencing the reproductive axes of birds.