PROGRAM PROJECT IN THE PATHOPHYSIOLOGY OF HUMAN GROWTH

该项目的总体目标是继续描述 儿童生长的生理学和病理生理学 科学和临床研究工作的结构和功能， 生长促进激素及其受体。 具体而言，我们的目标是： a）表征整个IGF I基因的结构和功能， 包括其启动子和调节区，通过以下方式确定机制： 哪种生长激素激活IGF I基因转录，并决定 基因的生长激素调节区的突变是否 导致生长障碍。 B）表征IGF基因在胎鼠肾中的表达， 明确胰岛素样生长因子在胚胎肾中的作用 发展 c）表征IGF I受体的结构修饰并定义 翻译后加工过程中功能结构域的形成 受体。 d）表征生长激素和胰岛素样生长的异常 因子结构和作用，包括生长激素和IGF的作用 I结合蛋白在各种生长类型的病理生理学中的作用 失败 e）量化每日能量消耗、身体蛋白质动态和葡萄糖 和氨基酸对胰岛素作用的敏感性， 儿童和评估这些变量之间的关系和急性 以及对生长激素治疗的慢性反应。

The overall goal of this project will be to continue to characterize the physiology and pathophysiology of childhood growth by a coordinated basic science and clinical research effort into the structure and function of growth promoting hormones and their receptor. Specifically, we aim to: a) Characterize the structure and function of the entire IGF I gene, including its promoter and regulatory regions, determine the mechanisms by which growth hormone activates IGF I gene transcription, and determine whether mutations in the growth hormone regulatory region of the gene are responsible for disorders of growth. b) Characterize the expression of the IGF genes in fetal rat kidney and define the roles of the insulin-like growth factors in embryonic kidney development. c) Characterize structural modifications of the IGF I receptor and define the formation of functional domains during post-translational processing of the receptor. d) Characterize abnormalities in growth hormone and insulin-like growth factor structure and action, including the roles of growth hormone and IGF I binding proteins in the pathophysiology of various types of growth failure. e) Quantify daily energy expenditure, body protein dynamics, and glucose and amino acid sensitivity to the actions of insulin in slowly growing children and assess the relationships between these variables and the acute and chronic responses to growth hormone treatment.