特发性矮小患儿生长激素-胰岛素样生长因子轴变化的研究

Disorder of the growth hormone/insulin-like growth factors axis in children with idiopathic short stature

目的观察特发性矮小(ISS)患儿血中生长激素(GH)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)及生长激素结合蛋白(GHBP)水平的变化。方法2002年6月至2006年5月在中南大学湘雅二医院儿科就诊的37例ISS患儿为病例组,37例年龄性别相匹配的正常儿童为对照组。采用放射免疫分析法(RIA)测定血清GH,免疫放射计量法(IRMA)测定血清IGF-1及IGFBP-3,葡聚糖覆盖炭末吸附法(DCT)检测血清GHBP。结果ISS组血清GHBP、IGF-1、IGFBP-3均明显低于对照组(均P<0.01),而血清GH基础值在ISS组明显高于对照组(P<0.05)。结论ISS患儿血中IGF-1和IGFBP-3降低可能是其矮小的原因之一。ISS患儿血中反映生长激素受体(GHR)水平的GHBP降低,而GH基础值升高,提示可能存在因GHR缺陷导致的GH不敏感。

Objective Idiopathic short stature（ISS）is a term used for children in whom the pathogenesis or aetiology of the short stature is undefined.The growth hormone（GH）-insulin-like growth factor-1（IGF-1）axis plays such a key role in regulating growth and development that people try to elucidate the relationship between the disturbance of the hormone,factors and signaling pathway in this endocritic axis and idiopathic short stature.However,the data in this field being heterogeneous and sometimes contradictory,further studies are necessary.To evaluate whether children with ISS had reduced concentration of serum IGF-1 and IGFBP-3,whether the decreased levels of serum IGF-1 and IGFBP-3 result from growth hormone insensitivity caused by deficiency of GHR,which correspond with levels of serum GHBP.Methods Thirty-seven children with idiopathic short stature（32 boys and 5 girls）and 37 age-and sex-matched normal-statured children were included in the study.The serum basal GH was measeured by specific radioimmunoassay,the serum IGF-1,IGFBP-3 were measeured by immunoradiometric analysis and GHBP was measeured by Dextran-coated charcoal technique.Results In comparison with normal subjects,ISS subjects had significantly lower serum values of GHBP,IGF-1 and IGFBP-3（P〈0.01）;however,ISS subjects had higher serum basal GH（P〈0.05）than normal controls.Conclusion Reduced concentration of serum IGF-1 and IGFBP-3 may be one of the causes that contribute to growth failure in children with ISS.The decreased levels of serum GHBP and elevated basal GH in children with ISS suggest that these children could have a growth hormone insensitivity resulting from GHR deficiency.