Ghrelin和脑功能

Ghrelin是首先从大鼠胃粘膜发现的一种新的脑-肠肽激素,具有促进生长激素释放的作用。它经辛酰化修饰具有生物学活性后可以通过血脑屏障发挥作用。研究发现,Ghrelin及其受体在脑组织(如下丘脑、大脑皮质、脑干、海马等)分布较广泛。近几年来,人们对Ghrelin和脑功能的研究也越来越多。本文就Ghrelin在学习和记忆、睡眠、焦虑、应激及神经保护等脑功能中所发挥的作用作一综述。     

脑肠肽Ghrelin-GHSR信号系统与肿瘤的关系

脑肠肽Ghrelin是一种含有28个氨基酸的生长激素释放肽,为生长激素促分泌素受体(growth hormone secretagogue recep-tor,GHSR)的内源性配体。Ghrelin及其功能性受体GHSR-1a广泛分布于中枢和外周组织。此外,在多种肿瘤组织和癌细胞中发现有Ghrelin及其功能性受体GHSR-1a的表达。我们的前期工作和目前的研究发现Ghrelin可与经典的功能性受体GHSR-1a或新型受体结合,通过激活多条信号转导通路,对肿瘤的生物学行为发挥重要的调控作用。因此,脑肠肽Ghrelin-GHSR信号系统可为肿瘤的临床诊断和预后评估发挥重要作用,并为肿瘤的分子治疗提供新靶点。     

Ghrelin与疼痛研究进展

Ghrelin为1999年从大鼠胃粘膜及下丘脑中发现的一种生长激素促分泌素受体(growth hor-mone secretagogue receptor,GHS-Rs)的天然配体,由28个氨基酸残基组成。Ghrelin广泛分布于机体的多个组织器官,如下丘脑、垂体、胃肠道、胰腺、心脏、性腺等。Ghrelin与其受体结合后,具有促进生长激素的释放、增加摄食、刺激胃蠕动和胃酸分泌,改善心血管等多种生物学作用。近年来有研究表明,Ghrelin在中枢神经系统具有广泛分布,并且具有镇痛作用,其主要通过调节与疼痛有关的系统和抑制促炎细胞因子的分泌进而缓解疼痛。现将Ghrelin在疼痛方面的研究做一综述。     

Ghrelin在细胞凋亡和焦亡中的作用

Ghrelin是一种新发现的脑-肠肽,具有多种生物学功能,可以调节细胞的增殖和存活等。近些年的研究表明凋亡和焦亡之间存在串话,在多个水平上相互联系,而Ghrelin通过调控凋亡和焦亡相关通路对多种疾病的发生发展产生影响。本文结合国内外研究就Ghrelin在细胞凋亡和焦亡中的作用作一综述。     

Ghrelin 发现和结构的研究现状

Ghrelin是生长激素促分泌素受体(growth hormone secretagogue receptor,GHSR)的内源性配体,是1999年由Kojima等[]人从大鼠胃组织中发现的含28个氨基酸的多肽,主要由胃黏膜泌酸腺X/A样细胞分泌并通过与其特异性受体结合而产生多种生物学效应。本文总结了近几年的文章,旨在通过对Ghrelin的发现和结构的介绍,为以后的相关研究奠定基础。     

Ghrelin发现和结构的研究现状

Ghrelin是生长激素促分泌素受体（growth hormone secretagogue receptor,GHSR）的内源性配体,是1999年由Kojima等人从大鼠胃组织中发现的含28个氨基酸的多肽,主要由胃黏膜泌酸腺X／A样细胞分泌并通过与其特异性受体结合而产生多种生物学效应。本文总结了近几年的文章,旨在通过对Ghrelin的发现和结构的介绍,为以后的相关研究奠定基础。     

Ghrelin对消化系统功能的调节

Ghrelin是一种生长激素促分泌物受体的内源性配体,具有刺激下丘脑和垂体前叶释放生长激素、增强食欲、调节能量平衡及促进胃酸分泌等作用。Ghrelin及其受体在下丘脑、垂体、肾、胃、胰腺、唾液腺中都有表达,可能是脑与胃肠道之间调节内分泌的一种介质,有望在诊断和治疗某些消化系统疾病中发挥一定的作用。本文就消化系统分泌的ghrelin的调节功能作一简要综述。     

Ghrelin与生殖系统研究进展

Ghrelin是1999年发现的生长激素促分泌素受体(growth hormone secretagogue receptor,GHS-R)的天然配体,由28个氨基酸残基组成.除具有促进生长激素的释放、增加摄食、刺激胃蠕动和胃酸分泌,尚有其它许多功能.近年来发现Ghrelin及其受体在生殖系统也广泛分布,提示Ghrelin对生殖系统也具有重要的调节作用,进一步的研究发现Ghrelin具有调节生殖激素黄体生成素、催乳素、雌二醇和孕酮的分泌,促进颗粒细胞的增殖等作用.本文就Ghrelin在生殖系统的研究进展做如下综述.     

Ghrelin在物质依赖中的研究进展

Ghrelin为1999年发现的一种脑肠肽,是生长激素促分泌素受体(growth hormone secretagogue receptor,GHS-R)的内源性配体。Ghrelin参与体内多种重要生理过程,能促进生长激素的释放、调节摄食和能量平衡。近来有研究表明ghrelin还可通过结合受体GHS-R1α作用于中脑多巴胺奖赏系统,对物质依赖产生影响。本文总结了ghrelin与不同成瘾物质包括酒精、尼古丁、中枢兴奋剂、大麻素和阿片类药物之间的关系,望有助于更好地理解和解决物质依赖问题。Ghrelin及其受体未来有望成为治疗物质依赖的新作用位点。     

生长激素促释放剂受体配体的研究进展

生长激素促释放剂是一种合成的小分子化合物,它通过生长激素促释放剂受体而起作用,该受体是一种新的G蛋白偶联受体。以前曾认为生长激素促释放剂受体是一种孤儿受体,直到近年来从人和鼠的胃中鉴定到Ghrelin的存在,而改变了这种看法。Ghrelin是包含28个氨基酸残基的肽,在3号位的丝氨酸位点有辛酰化基团。该肽是在X／A样细胞分泌颗粒中发现的,Ghrelin的发现表明促垂体分泌生长激素可能不止受到来自下丘脑的生长激素释放激素的调节,同时还可能受到来自胃和下丘脑的Ghrelin的调节。     

Ghrelin,CGRP,NT对胃肠作用的研究进展

胃肠道是人体内最大的激素分泌器官,是调节肽即胃肠激素最丰富的来源。胃肠激素与胃肠功能有很大关系,它们与神经系统一起,共同调节消化器官的运动、分泌和吸收及其他多种功能。促生长素(Ghrelin)、降钙素基因相关肽(CGRP)和神经降压素(NT)是近年来新发现的胃肠激素中的代表。Ghrelin主要由胃组织产生,可以促进胃肠蠕动,还可促进胃酸分泌,这些作用是由迷走神经所介导的,ghrelin还具有对消化道粘膜的保护作用,此作用受多种方式调控。CGRP广泛分布于中枢和外周神经系统,有调节胃肠血流、胃肠分泌及胃肠运动等多种功能,目前学者普遍认为CGRP这些生物学效应的发挥是通过一氧化氮(NO)及前列腺素(PG)介导的。NT广泛分布于脑和胃肠道及其它组织中,由肠道N细胞分泌,能够抑制胃肠运动,对胃肠黏膜细胞具有保护作用,这些作用是迷走神经、调节肽等多种途径介导的。随着对这三种胃肠激素的深入了解,人们将对人体胃肠道疾病产生更加深刻的认识。本文就近年来对Ghrelin、CGRP、NT对胃肠作用的研究作一综述。     

Ghrelin system in Alzheimer's disease

Alzheimer's disease (AD) is the most common type of dementia in seniors. Current efforts to understand the etiopathogenesis of this neurodegenerative disorder have brought forth questions about systemic factors in the development of AD. Ghrelin is a brain–gut peptide that is activated by ghrelin O-acyltransferase (GOAT) and signals via its receptor, growth hormone secretagogue receptor (GHSR). With increasing recognition of the neurotropic effects of ghrelin, the role of ghrelin system deregulation in the development of AD has been accentuated in recent years. In this review, we summarized recent research progress regarding the mechanisms of ghrelin signaling dysregulation and its contribution to AD brain pathology. In addition, we also discussed the therapeutic potential of strategies targeting ghrelin signaling for the treatment of this neurological disease.     

Ghrelin -- a new endogenous growth hormone secretagogue

Ghrelin is a new endogenous peptide, discovered in 1999 by Kojima et al., as the result of a search for an endogenous ligand for an orphan receptor of known structure and function. Ghrelin is composed of 28 amino acids and is produced mostly by cells of the stomach, hypothalamus, and hypophysis, but it has also been detected in other tissues. Its discovery is related to the development of a new hypothesis regarding the regulation of growth hormone secretion. It is an antagonist of somatostatin. Ghrelin activates the release of growth hormone from the somatotrophic cells of the hypophysis. It participates in the regulation of energy homeostasis, increases food intake, decreases energy output and exerts a lipogenetic effect. Its metabolic effects do not depend on the GH/IGF-I system, but are mediated by the NPY/Y1 and AGRP receptor system. Ghrelin influences the secretion and motility of the gastrointestinal tract, especially the stomach. The presence of ghrelin and its receptors has also been demonstrated in many other tissues. Its function in these tissues has not yet been studied, thus providing many possibilities for further research.     

Endocrine and non-endocrine actions of ghrelin

Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amounts were detected in bowel, pancreas, kidneys, the immune system, placenta, testes, pituitary, and hypothalamus. Ghrelin displays strong growth hormone (GH)-releasing action mediated by the activation of the so-called GH secretagogue (GHS) receptor (GHS-R) type 1a. GHS-R are concentrated in the hypothalamus-pituitary unit but are also distributed in other central and peripheral tissues. Apart from the potent GH-releasing action, ghrelin has other actions including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, influence on exocrine and endocrine pancreatic function as well as on glucose metabolism, cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system. The discovery of ghrelin opened many new perspectives of research in neuroendocrinology and metabolism, and even also in other fields of internal medicine as gastroenterology, immunology, oncology and cardiology. The possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact is obviously suggested and is receiving great attention.     

The role of growth hormone in neural development

Growth hormone (GH) is integrally involved in the development of the central nervous system (CNS), as well as during its recovery from injury, two processes that share many similarities and may influence CNS functionality. This review discusses some of the most recent findings in the field and, in particular, the ontogeny, distribution, regulation and putative functions of GH and its receptor within the CNS, particularly during development. The relative roles of peripheral GH, acting in part through insulin-like growth factor-I, and of the autocrine/paracrine GH system within the brain are considered. The potential role of GH as a therapeutic agent to influence brain development and function is discussed.     

Structure, distribution and physiological functions of ghrelin in fish

Ghrelin was originally purified and characterized in rats and humans as the first identified endogenous ligand of the growth hormone secretagogue receptor. In mammals, ghrelin is mainly produced in the stomach, with minor levels of ghrelin present in the brain and various other tissues. Ghrelin is involved in the regulation of many physiological functions including the regulation of growth hormone secretion and food intake in mammals. The gene and peptide structures of ghrelin have been recently identified in several fish species. As in mammals, ghrelin mRNA is mainly expressed in the gut of fish. Ghrelin is involved in the regulation of a number of physiological functions, including the regulation of pituitary hormone release and the stimulation of food intake in fish. In this review, we wish to provide an up-to-date discussion on the structure, distribution and functions of ghrelin in fish, in comparison to ghrelin in other vertebrates.     

Ghrelin acylation and metabolic control

Since its discovery, many physiologic functions have been ascribed to ghrelin, a gut derived hormone. The presence of a median fatty acid side chain on the ghrelin peptide is required for the binding and activation of the classical ghrelin receptor, the growth hormone secretagogue receptor (GHSR)-1a. Ghrelin O-acyl transferase (GOAT) was recently discovered as the enzyme responsible for this acylation process. GOAT is expressed in all tissues that have been found to express ghrelin and has demonstrated actions on several complex endocrine organ systems such as the hypothalamus-pituitary-gonadal, insular and adrenal axis as well as the gastrointestinal (GI) tract, bone and gustatory system. Ghrelin acylation is dependent on the function of GOAT and the availability of substrates such as proghrelin and short- to medium-chain fatty acids (MCFAs). This process is governed by GOAT activity and has been shown to be modified by dietary lipids. In this review, we provided evidence that support an important role of GOAT in the regulation of energy homeostasis and glucose metabolism by modulating acyl ghrelin (AG) production. The relevance of GOAT and AG during periods of starvation remains to be defined. In addition, we summarized the recent literature on the metabolic effects of GOAT specific inhibitors and shared our view on the potential of targeting GOAT for the treatment of metabolic disorders such as obesity and type 2 diabetes.