How to Contribute to the Progress of Comparative Endocrinology: Discovery of GnIH and Progress and Prospect of GnIH Research
Kazuyoshi Tsutsui
Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo 162-8480, Japan, [email protected]
Obtaining new insights by discovering novel neuropeptides regulating pituitary and brain functions is essential for the progress of comparative endocrinology and neuroendocrinology. At the beginning of the 1970s, Schally’s and Guillemin’s groups discovered gonadotropin-releasing hormone (GnRH), a hypothalamic neuropeptide known to stimulate the release of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from gonadotropes in the anterior pituitary of mammals. Subsequently, several GnRHs have been identified in other vertebrates. Based on extensive studies of GnRH over the next three decades, it was assumed that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in mammals and other vertebrates. In 2000, however, Tsutsui’s group challenged this notion with the discovery of gonadotropin-inhibitory hormone (GnIH), a hypothalamic neuropeptide that actively inhibits gonadotropin release, in quail. Subsequently, Tsutsui’s studies demonstrated that GnIH is highly conserved among vertebrates, from agnathans to humans, acting as a key player regulating reproduction. Following intensive research showed that GnIH inhibits gonadotropin synthesis and release through actions on GnRH neurons and gonadotropes via GPR147 in birds and mammals. As in birds and mammals, fish GnIH peptides inhibit gonadotropin release, indicating the conserved inhibitory role of GnIH in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. Thus, we now know that GnRH is not the sole hypothalamic neuropeptide controlling vertebrate reproduction. In addition, recent studies by Tsutsui’s group have demonstrated that GnIH has important functions beyond the control of reproduction. Based on these findings, it now appears that GnIH acts on the pituitary and the brain to affect a number of behaviors, including reproductive behavior through changes in neurosteroid biosynthesis in the brain. Thus, the following 17 years of GnIH research in collaboration with world's leading laboratories has permitted a more complete understanding of the neuroendocrine control of reproductive physiology and behavior. This opening lecture summarizes the discovery of GnIH and the progress and prospect of GnIH Research in this new research field.
Kazuyoshi Tsutsui
Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, and Center for Medical Life Science of Waseda University, Tokyo 162-8480, Japan, [email protected]
Obtaining new insights by discovering novel neuropeptides regulating pituitary and brain functions is essential for the progress of comparative endocrinology and neuroendocrinology. At the beginning of the 1970s, Schally’s and Guillemin’s groups discovered gonadotropin-releasing hormone (GnRH), a hypothalamic neuropeptide known to stimulate the release of both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from gonadotropes in the anterior pituitary of mammals. Subsequently, several GnRHs have been identified in other vertebrates. Based on extensive studies of GnRH over the next three decades, it was assumed that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in mammals and other vertebrates. In 2000, however, Tsutsui’s group challenged this notion with the discovery of gonadotropin-inhibitory hormone (GnIH), a hypothalamic neuropeptide that actively inhibits gonadotropin release, in quail. Subsequently, Tsutsui’s studies demonstrated that GnIH is highly conserved among vertebrates, from agnathans to humans, acting as a key player regulating reproduction. Following intensive research showed that GnIH inhibits gonadotropin synthesis and release through actions on GnRH neurons and gonadotropes via GPR147 in birds and mammals. As in birds and mammals, fish GnIH peptides inhibit gonadotropin release, indicating the conserved inhibitory role of GnIH in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. Thus, we now know that GnRH is not the sole hypothalamic neuropeptide controlling vertebrate reproduction. In addition, recent studies by Tsutsui’s group have demonstrated that GnIH has important functions beyond the control of reproduction. Based on these findings, it now appears that GnIH acts on the pituitary and the brain to affect a number of behaviors, including reproductive behavior through changes in neurosteroid biosynthesis in the brain. Thus, the following 17 years of GnIH research in collaboration with world's leading laboratories has permitted a more complete understanding of the neuroendocrine control of reproductive physiology and behavior. This opening lecture summarizes the discovery of GnIH and the progress and prospect of GnIH Research in this new research field.