在儿童矮小症诊治中的应用（初稿）课件_1.pptx

IGF-1在儿童矮小症诊治中应用的过去、现在与未来安科生物袁牧2014.9.9主要内容历史年份事件1957IGF-1 and IGF-2 were identified by Salmon and Daughadayand designated “sulphation factor” by their ability to stimulate 35-sulphate incorporation into rat cartilage. [1]1963Froesch et al described the non-suppressible insulin-like activity (NSILA) of two soluble serum components (NSILA I and II)[2]1972The labels sulphation factor and NSILA were replaced by the term “somatomedin”, denoting a substance under control and mediating the effects of GH. [2]1976Rinderknecht and Humbel isolated two active substances from human serum, which owing to their structural resemblance to proinsulin were renamed “insulin-like growth factor 1 and 2” (IGF-1 and 2). [3]1988The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS.1.J Lab Clin Med 1957;49:825–362.J Clin Invest 1963;42:1816–343. Proc Natl Acad Sci U S A 1976;73:2365–9.The cascade of the growth hormone axisFigure 1The cascade of the growth hormone axis. CNS, central nervous system; GH,growth hormone;GHBP,GH binding protein; GH-S,GH secretagogues; IGF-1,insulin-like growth factor 1; IGFBPs, IGF binding proteins; +, stimulation; –, inhibition.IGF-1基因The IGF-1 gene is on the long arm of chromosome 12q23–23. The human IGF-1 gene consists of six exons, including two leader exons, and has two promoters.Figure 2Type 1 insulin-like growth factor receptor gene and mRNA. Reproduced with permission from WernerIGF binding proteins (IGFBPs) In the plasma, 99% of IGFs are complexed to a family of binding proteins, which modulate the availability of free IGF-1 to the tissues. There are six binding proteins.In humans, almost 80% of circulating IGF-1 is carried by IGFBP-3, a ternary complex consisting of one molecule of IGF-1, one molecule of IGFBP-3,and one molecule of an 88 kDa protein named acid labile subunit. IGFBP-1 is regulated by insulin and IGF-1; IGFBP-3 is regulated mainly by GH but also to some degree by IGF-1. IGF-1受体Figure 3Re