Growth hormone as an autocrine/paracrine factor in chick embryogenesis: an retinal model

生长激素作为鸡胚胎发生中的自分泌/旁分泌因子：视网膜模型

• 批准号: 3617-2007
• 负责人: Harvey, Stephen
• 金额: $ 6.18万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=366037
• 关键词: Growth; hormone; autocrine; paracrine; factor

This proposal is an extension of an ongoing program of research on the physiology of GH secretion and action. In postnatal development, GH is secreted from the pituitary gland (at the base of the brain) into the bloodstream, through which it gains access to every tissue in the body. These tissues express receptors that mediate the actions of pituitary GH on cellular growth and differentiation. However, while these 'endocrine' actions of pituitary GH are obligatory for postnatal development, embryonic or fetal growth is thought to be a 'growth-without-GH-syndrome', since it occurs prior to the development of the circulatory system and the differentiation of the pituitary gland. Embryonic or fetal growth is thus thought to be induced locally by tissue growth factors. Growth in the embryo may not, however, be 'paradoxical' since it may be mediated by local actions of GH produced in early embryonic tissues.    The applicant has recently discovered that GH gene expression is not confined to the pituitary gland and occurs almost ubiquitously in tissues of the chick embryo. 'Autocrine' or 'paracrine' actions of GH (actions in GH-producing cells or neighboring cells, respectively) may therefore regulate embryonic growth.    In the studies proposed, the applicant will increase or decrease GH status in the neural retina and retinal ganglion cells (RGCs) of early chick embryos and determine its effects on retinal function and retinal development. Specifically, the effects of retinal GH excess and deficiency on cell survival, proliferation, migration, neurite outgrowth, angiogenesis and synaptogenesis will be determined. The possibility that these actions may be direct or mediated via insulin-like-growth factor (IGF)-1, another tissue growth factor implicated in the 'endocrine' actions of pituitary GH, will also be assessed. The factors regulating retinal GH production or secretion will also be determined. These studies will provide a model for understanding the secretion and action of GH during embryonic or fetal growth, particularly in retinal and neural development.

这一建议是对生长激素分泌和作用的生理研究正在进行的计划的延伸。在出生后的发育过程中，生长激素从脑垂体（位于大脑底部）分泌到血液中，并通过血液进入身体的每一个组织。这些组织表达介导垂体GH对细胞生长和分化的作用的受体。然而，虽然垂体GH的这些“内分泌”作用对出生后发育是必需的，但胚胎或胎儿生长被认为是一种“无GH生长综合征”，因为它发生在循环系统发育和垂体分化之前。因此，胚胎或胎儿生长被认为是由组织生长因子局部诱导的。然而，胚胎中的生长可能不是“矛盾的”，因为它可能是由早期胚胎组织中产生的生长激素的局部作用介导的。申请人最近发现生长激素基因的表达不仅局限于脑垂体，而且在鸡胚的组织中几乎无处不在。因此，生长激素的“自分泌”或“旁分泌”作用（分别在GH产生细胞或邻近细胞中的作用）可能调节胚胎生长。在拟议的研究中，申请人将增加或减少早期鸡胚胎神经视网膜和视网膜神经节细胞（RGCs）中的GH状态，并确定其对视网膜功能和视网膜发育的影响。具体来说，视网膜生长激素过量和缺乏对细胞存活、增殖、迁移、神经突生长、血管生成和突触发生的影响将被确定。还将评估这些作用可能是直接的或通过胰岛素样生长因子(IGF)-1介导的，IGF -1是另一种与垂体GH的“内分泌”作用有关的组织生长因子。调节视网膜生长激素产生或分泌的因素也将被确定。这些研究将为理解生长激素在胚胎或胎儿生长过程中的分泌和作用，特别是在视网膜和神经发育过程中提供一个模型。