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Study of growth hormone receptor abnormalities in short children

矮个子儿童生长激素受体异常的研究

基本信息

批准号：
02671112
负责人：
HIZUKA Naomi
金额：
$ 1.47万
依托单位：
Tokyo Women's Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02671112/
关键词：
growth hormone (GH)GH receptor GH binding protein (GHBP)short stature 成長ホルモン

项目摘要

Recently it has been reported that serum GH binding protein (GHBP) is a extracellular hormone binding domain of the GH receptor. Therefore, the measurement of serum GHBP may be useful to evaluate GH receptor in vivo. At present, gel filtration method is used for measurement of serum GHBP, but by this method multiple samples could not be measured simultaneously. We have developed a simple method for measurement of serum GHBP using anti-GH receptor antibody. Binding of ^<125>I-hGH to human serum GHBP was immunoprecipitated with monoclonal anti-GH receptor antibody (GHRAB : * 263 ; AGEN Biomedical Ltd, QLD, Australia) that did not inhibit hGH binding to human serum GHBP. Serum GHBP in various clinical conditions was measured by this method, and the results were expressed'as percent specific binding relative to an adult reference serum. Serum GHBP values in normal adult males, normal adult females, patients with GH deficiency and patients with acromegaly were 87.5<plus-minus>9.7, 74.3<plus-minus>5.3, 106.3<plus-minus>5.2, and 35.4<plus-minus>4.4%, respectively, suggesting that GHBP is regulated by endogenous GH. Scatchard analysis of the bindings, carried out with correction made for endogenous serum GH, revealed that changes of the binding were mainly due to the changes of binding capacity. Furthermore, the serum GHBP values in patients with liver cirrhosis and poor nutritional conditions, and in some short children and those in late pregnant women and patients with ossification of the posterior longitudinal ligament (OPLL) were elevated From the above data, we conclude that this method could be practical to evaluate GH receptor in various clinical conditio

近年来研究发现，血清GH结合蛋白（GHBP）是GH受体的细胞外激素结合结构域。因此，血清GHBP的测定可能有助于体内GH受体的评价。目前，血清GHBP的测定多采用凝胶过滤法，但该方法不能同时测定多个样品。我们建立了一种用抗GH受体抗体测定血清GHBP的简便方法。用<125>不抑制hGH与人血清GHBP结合的单克隆抗GH受体抗体（GHRAB：* 263 ;阿根Biomedical Ltd，QLD，Australia）免疫沉淀β I-hGH与人血清GHBP的结合。用这种方法测定了各种临床条件下的血清GHBP，结果表示为相对于成人参考血清的特异性结合百分比。正常成年男性、正常成年女性、GH缺乏症患者和肢端肥大症患者的血清GHBP值分别为87.5 <plus-minus>± 9.7%、74.3 <plus-minus>± 5.3%、106.3 ± <plus-minus>5.2%和35.4 ± <plus-minus>4.4%，表明GHBP受内源性GH调节。结合的Scatchard分析，进行了内源性血清GH的校正，揭示了结合的变化主要是由于结合能力的变化。肝硬化、营养不良、矮小儿、晚孕妇女及后纵韧带骨化症患者血清GHBP值均升高。提示本法可用于各种临床情况下GH受体的测定。