Laboratory of Integrative Brain Sciences, Department of Biology, Waseda University, Center for Medical Life Science of Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Front Neuroendocrinol. 2010 Jul;31(3):284-95. doi: 10.1016/j.yfrne.2010.03.001. Epub 2010 Mar 6.
Identification of novel neurohormones that regulate the reproductive axis is essential for the progress of neuroendocrinology. The decapeptide gonadotropin-releasing hormone (GnRH) is the primary factor responsible for the hypothalamic control of gonadotropin secretion. Gonadal sex steroids and inhibin modulate gonadotropin secretion via feedback from the gonads, but a neuropeptide that directly inhibits gonadotropin secretion was unknown in vertebrates until 2000 when a hypothalamic dodecapeptide serving this function was discovered in quail. Because of its action on cultured pituitary in quail, it was named gonadotropin-inhibitory hormone (GnIH). GnIH acts on the pituitary and on GnRH neurons in the hypothalamus via a novel G protein-coupled receptor (GPR147). GPR74 may also be a possible candidate GnIH receptor. GnIH decreases gonadotropin synthesis and release, inhibiting gonadal development and maintenance. Melatonin stimulates the expression and release of GnIH via melatonin receptors expressed by GnIH neurons. GnIH actions and interactions with GnRH seem common not only to several avian species, but also to mammals. Thus, GnIH is considered to have an evolutionarily conserved role in controlling vertebrate reproduction, and GnIH homologs have also been identified in the hypothalamus of mammals. As in birds, mammalian GnIH homologs act to inhibit gonadotropin release in several species. More recent evidence in birds and mammals indicates that GnIH may operate at the level of the gonads as an autocrine/paracrine regulator of steroidogenesis and gametogenesis. Importantly, GnIH in birds and mammals appears to act at all levels of the hypothalamo-pituitary-gonadal (HPG) axis, and possibly over different time-frames (minutes-days). Thus, GnIH and its homologs appear to act as key neurohormones controlling vertebrate reproduction. The discovery of GnIH has enabled us to understand and manipulate vertebrate reproduction from an entirely new perspective.
鉴定调控生殖轴的新型神经激素对于神经内分泌学的发展至关重要。十肽促性腺激素释放激素（GnRH）是下丘脑控制促性腺激素分泌的主要因素。性腺性激素和抑制素通过来自性腺的反馈来调节促性腺激素的分泌，但是直到 2000 年，在鹌鹑中发现了一种具有这种功能的下丘脑十二肽，才发现了一种直接抑制促性腺激素分泌的神经肽。由于其在鹌鹑培养的垂体中的作用，它被命名为促性腺激素抑制激素（GnIH）。GnIH 通过一种新型的 G 蛋白偶联受体（GPR147）作用于垂体和下丘脑的 GnRH 神经元。GPR74 也可能是 GnIH 受体的候选者。GnIH 减少促性腺激素的合成和释放，抑制性腺的发育和维持。褪黑素通过 GnIH 神经元表达的褪黑素受体刺激 GnIH 的表达和释放。GnIH 的作用及其与 GnRH 的相互作用不仅在几种禽类中很常见，在哺乳动物中也很常见。因此，GnIH 被认为在控制脊椎动物生殖方面具有进化上保守的作用，并且在哺乳动物的下丘脑也鉴定出了 GnIH 同源物。与鸟类一样，几种哺乳动物的 GnIH 同源物也可作用于抑制几种物种的促性腺激素释放。鸟类和哺乳动物的最新证据表明，GnIH 可能作为类固醇生成和配子发生的自分泌/旁分泌调节剂在性腺中起作用。重要的是，鸟类和哺乳动物中的 GnIH 似乎在整个下丘脑-垂体-性腺（HPG）轴的各个水平起作用，并且可能在不同的时间范围内起作用（数分钟至数天）。因此，GnIH 及其同源物似乎作为控制脊椎动物生殖的关键神经激素起作用。GnIH 的发现使我们能够从全新的角度理解和操纵脊椎动物的生殖。
