Regulation of the synthesis and release of pituitary hormones by novel hypothalamic neurohormones

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Probing undiscovered neuropeptides that play important roles in the regulation of pituitary function in vertebrates is essential for the progress of neuroendocrinology. In this research, We identified a novel hypothalamic neuropeptide with a C-terminal LPLRF-amide sequence in the quail brain. This avian neuropeptide was, shown to be located in the hypothalamo-hypophysial system and to decrease gonadotropin release. We therefore designated this novel neuropeptide as 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. Thus, GnIH acts directly on the pituitary via GnIH receptor to inhibit gonadotropin 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. Subsequently, we further identified novel hypothalamic neuropeptides closely related to GnIH in the brains of other vertebrates, such as mammals, amphibians, and fish. The identified neuropeptides possessed a LPXRF-amide (X = L or Q) motif at 'their C-termini. These GnIH homologous peptides (LPXRF-amide peptides) also were localized in the hypothalamus and other brainstem areas and regulated the release of gonadotropins and prolactin. Thus, GnIH and GnIH homologous peptides are key factors controlling vertebrate reproduction.