1、主要内容IGF-1的 历 史与 简 介IGF-1在矮小症 诊 断中 应 用的研究 现 状IGF-1在矮小症 GH治 疗监测 中 应 用的研究 现 状IGF-1作 为药 物治 疗 矮小症的研究 现 状IGF-1临 床 应 用的未来历史年份 事件1957 IGF-1 and IGF-2 were identified by Salmon and Daughadayand designated “sulphation factor” by their ability to stimulate 35-sulphate incorporation into rat cartilage. 11963 Fr
2、oesch et al described the non-suppressible insulin-like activity (NSILA) of two soluble serum components (NSILA I and II)21972 The labels sulphation factor and NSILA were replaced by the term “somatomedin”, denoting a substance under control and mediating the effects of GH. 21976 Rinderknecht and Hu
3、mbel 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). 31988 The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS.1.J Lab Clin
4、Med 1957;49:82536 2.J Clin Invest 1963;42:1816343. Proc Natl Acad Sci U S A 1976;73:23659.The cascade of the growth hormone axisThe 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; I
5、GFBPs, IGF binding proteins; +, stimulation; , inhibition.Figure 1IGF-1基因Type 1 insulin-like growth factor receptor gene and mRNA. Reproduced with permission from WernerThe IGF-1 gene is on the long arm of chromosome 12q2323. The human IGF-1 gene consists of six exons, including two leader exons, an
6、d has two promoters.Figure 2IGF 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
7、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Resemblance between the insulin and insulin-like
8、 growth factor 1 (IGF-1) receptorsFigure 3GH刺激试验的局限性 药物刺激试验不是生理过程 ,不能反映生理状态下的 GH分泌情况 GH刺激试验的重复性差 GH刺激试验准确性差 影响 GH刺激试验的因素较多 ,患者的年龄、性发状态以及刺激药物、 GH检测方法等会影响试验的结果 不能根据 GH刺激试验预测患者对 rhGH治疗的反应 部分药物刺激试验有一定的副作用IGF-I和 IGFBP-3测定 由于药物刺激试验存在较高的假阳性率 ,不能很好地反映 GH分泌情况 ,而血中IGF-1和 IGFBP-3水平相当稳定 ,无明显脉冲式分泌和昼夜节律变化 ,因此能较好地
9、反映内源性生长激素分泌状态。 临床研究显示 1-4： IGF-1和 IGFBP-3浓度与 GH峰值相关 ,但离散度较大 ;而 IGFBP-3水平在两组中差异无统计学意义 ,仅 IGF-1浓度与 GHD组呈显著相关 如矮身材儿童的病史 ,临床症状和体格检查等数据不能排除 GH 分泌不足时 ,应选择血清 IGF-1 和 IGFBP-3的测定作为筛查 1 : IGF-1和 IGFBP-3水平在正常范围的第 5百分位上 ,可排除 GHD,不需要作进一步试验 IGF-1低于第 1百分位 , IGFBP-3低于第 5百分位 ,除进行 GH-IGF轴检查外 ,还需进行全面系统检查 IGF-1水平低于第 10
10、百分位 , IGFBP-3水平低于第 20百分位 ,则不能排除GH2IGF轴功能异常。 对所有 IGF-1和 IGFBP-3低水平者 ,则必须进行 GH刺激试验 ,如 GH有正常响应时 ,应疑为 GH不敏感综合征 (GH insensitivity syndrom, GHIS) ,需进行 IGF 生成试验1.Ranke MB.Diagnostics of Endocrine function in children andadolescents.Basel:Karger,2003.12.中国实用儿科杂志 ,1999,14:89-91. 3.中华内分泌代谢杂志 ,1999,15:125-126.4.实用医学杂志 ,2002,18:1100-1101不同年龄组健康人血清 IGF-1水平 (g/L)1.Ranke MB.Diagnostics of Endocrine function in children andadolescents.Basel:Karger,2003.1不同年龄组健康人血清 IGFBP-3正常值 (mg/L) 1.Ranke MB.Diagnostics of Endocrine function in children andadolescents.Basel:Karger,2003.1
