PROGRAM PROJECT IN THE PATHOPHYSIOLOGY OF HUMAN GROWTH

该项目的长期目标是描述 孩子们既能正常成长，又不能实现 正常身材 根据常规临床分类 特征、生长激素和IGF I分泌标准：（1）潜力 将寻找hGH和IGF I基因的突变， 围绕这些基因进行研究，并研究这些基因的调控。 (2)循环hGH和IGF肽中的结构异常将被 特征及其受体亲和力和生物活性 量化。 (3)将描述hGH受体的结构缺陷 以及IGF的寡糖单元结构、生物合成和周转 受体决定。 (4)可能的异常受体后事件将是 定义，和（5）在体内的意义和临床后果 将用多面稳定同位素研究这些扰动 蛋白质合成代谢和分解代谢对外源性 生长激素管理。

The long-term objective of this program project is to characterize mechanisms by which children both grow appropriately and fail to achieve normal stature. Following classification by conventional clinical characteristics, growth hormone and IGF I secretory criteia: (1) potential mutations in hGH and IGF I genes will be sought, polymorphism within and around these genes examined, and the regulation of these genes studied. (2) Structural abnormalities in circulating hGH and IGF peptides will be characterized and their receptor affinities and biologic activities quantified. (3) Structural defects of the hGH receptor will be delineated and the oligosaccharide unit structure, biosynthesis, and turnover of IGF receptors determined. (4) Possible aberrant post-receptor events will be defined, and (5) The in vivo significance and clinical consequences of these disturbances will be investigated with multi-faceted stable-isotope kinetic probes of protein anabolic and catabolic responses to exogenous growth hormone administration.