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

探索在脊椎动物垂体功能调节中起重要作用的未被发现的神经肽对神经内分泌学的发展至关重要。在这项研究中，我们在鹌鹑大脑中鉴定了一种具有c端lplrf -酰胺序列的新型下丘脑神经肽。这种鸟类神经肽被证明位于下丘脑-垂体系统，并减少促性腺激素的释放。因此，我们将这种新型神经肽命名为促性腺激素抑制激素（GnIH）。为了阐明GnIH的作用模式，我们在鹌鹑中鉴定了一种新的G蛋白偶联受体。GnIH受体具有7个跨膜结构域，特异结合GnIH。GnIH受体在垂体和包括下丘脑在内的几个大脑区域表达。因此，GnIH通过GnIH受体直接作用于垂体，抑制促性腺激素的释放。为了证明GnIH的功能意义及其作为鸟类繁殖关键调控神经肽的潜在作用，我们研究了GnIH在鹌鹑性腺发育和维持中的作用。慢性GnIH治疗通过减少促性腺激素的合成和释放来抑制性腺的发育和维持。在麻雀和鸡等其他鸟类的下丘脑中也发现了GnIH，并抑制促性腺激素的合成和释放。随后，我们进一步在其他脊椎动物（如哺乳动物、两栖动物和鱼类）的大脑中发现了与GnIH密切相关的新型下丘脑神经肽。所鉴定的神经肽在其c端具有LPXRF-amide （X = L或Q）基序。这些GnIH同源肽（lpxrf -酰胺肽）也定位于下丘脑和其他脑干区域，并调节促性腺激素和催乳素的释放。因此，GnIH和GnIH同源肽是控制脊椎动物繁殖的关键因素。

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.