Study of growth hormone receptor abnormalities in short children

最近有报道称，血清生长激素结合蛋白(GHBP)是生长激素受体的一个细胞外激素结合域。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的测定主要采用凝胶过滤法，但这种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。用不抑制hGH与人血清GHBP结合的抗GH受体的单抗(Ghrab：*263；Agen Biomedical Ltd，QLD，Australia)免疫沉淀hGH与人血清GHBP的结合。用该方法测定了不同临床条件下的血清GHBP，结果以与成人参考血清的特异性结合百分比表示。正常成年男性、正常成年女性、生长激素缺乏症患者和肢端肥大症患者的血清GHBP值分别为87.59.7、74.3lt；+-5.35.3、106.3&lt；+-5.2%和35.4%-4.4%。结合Scatchard分析，并对内源性血清GH进行校正，发现结合的变化主要是由于结合容量的变化。此外，在营养不良的肝硬变患者、一些矮小的儿童、妊娠晚期妇女和后纵韧带骨化患者的血清GHBP值升高，我们认为该方法可用于不同临床条件下的GH受体的检测。

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