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

新型下丘脑神经激素对垂体激素合成和释放的调节

• 批准号: 15207007
• 负责人: TSUTSUI Kazuyoshi
• 金额: $ 25.63万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15207007/
• 关键词: hypothalamic neurohormones; GnIH; GnIH homologOus peptides; GnIH receptor; pituitary hormones; gonadotropin; prolactin; reproduction; 生殖腺刺激ホルモン放出抑制ホルモン(GnIH); 視床下部ニューロン; メラトニン; 新規視床下部ペプチド; ゴナドトロピン; 成長ホルモン; ゴナドトロピン放出抑制ホルモン; 成長ホルモン放出促進ペプチド

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.

探索在脊椎动物垂体功能调节中起重要作用的神经肽对神经内分泌学的发展至关重要。在本研究中，我们在鹌鹑脑中鉴定了一种新的下丘脑神经肽，其C-末端为LPLRF-酰胺序列。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，我们将这种新的神经肽命名为促性腺激素抑制激素（GnIH）。为了阐明GnIH的作用方式，我们在鹌鹑中鉴定了一种新的G蛋白：GnIH的偶联受体。GnIH受体具有七个跨膜结构域，并特异性结合GnIH。GnIH受体在垂体和包括下丘脑在内的几个脑区中表达。因此，GnIH通过GnIH受体直接作用于垂体以抑制促性腺激素释放。为了证明GnIH的功能意义及其作为鸟类生殖关键调节神经肽的潜在作用，我们研究了GnIH对鹌鹑性腺发育和维持的作用。GnIH长期治疗通过减少促性腺激素的合成和释放抑制性腺发育和维持。GnIH也存在于其他鸟类的下丘脑中，包括麻雀和鸡，也抑制促性腺激素的合成和释放。随后，我们进一步确定了新的下丘脑神经肽密切相关的GnIH在其他脊椎动物的大脑，如哺乳动物，两栖动物和鱼类。所鉴定的神经肽在其C-末端具有LPXRF-酰胺（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生殖的关键因素。

项目成果

Mode of action and functional significance of avian gonadotropin-inhibitory hormone (GnIH): a review.

• DOI: 10.1002/jez.a.305
• 发表时间: 2006-09
• 期刊: Journal of experimental zoology. Part A, Comparative experimental biology
• 作者: K. Tsutsui;T. Ubuka;H. Yin;T. Osugi;K. Ukena;G. Bentley;N. Ciccone;Kazuhiko Inoue;V. S. Chowdhury;P. Sharp;J. Wingfield

A novel G protein-coupled receptor for gonadotropin-inhibitory hormone in the Japanese quail (Coturnix japonica):: identification, expression and binding activity

• DOI: 10.1677/joe.1.05926
• 发表时间: 2005-01-01
• 期刊: JOURNAL OF ENDOCRINOLOGY
• 影响因子: 4
• 作者: Yin, H;Ukena, K;Tsutsui, K
• 通讯作者: Tsutsui, K

Characterization of crustacean cardioactive peptide as a novel insect midgut factor: isolation, localization, and stimulation of alpha-amylase activity and gut contraction.

• DOI: 10.1210/en.2004-0722
• 发表时间: 2004-12
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: T. Sakai;H. Satake;H. Minakata;M. Takeda

Salusin beta is a surrogate ligand of the mas-like G protein-coupled receptor MrgA1.

• 发表时间: 2006
• 期刊: European journal of pharmacology
• 影响因子: 5
• 作者: Zhiwei Wang;Toshio Takahashi;Yumiko Saito;H. Nagasaki;N. K. Ly;H. Nothacker;R. Reinscheid;Jun Yang;J. Chang;M. Shichiri;O. Civelli

Review : Gonadotropin-Inhibitory Hormone (GnIH) : Discovery, Progress and Perspective.

评论：促性腺激素抑制激素 (GnIH)：发现、进展和展望。

• 发表时间: 2006
• 期刊: J. Poult. Sci. 43
• 作者: K.Tsutsui