Endo Y
Department of Laboratory Medicine, Osaka University Medical School.
Rinsho Byori. 1990 Oct;38(10):1149-54.
Thyroid-stimulating hormone (TSH) is a member of a family of heterodimeric glycoprotein hormones which have a common alpha-subunit but differ in their hormone-specific beta-subunit. To date, numerous studies have been carried out to elucidate the structure-function relationship of glycoprotein hormones and molecular mechanism of hormone action. On the other hand, several types of abnormality in the structure and function of glycoprotein hormones, as well as TSH, have been observed in clinical samples, especially in malignant diseases. To approach the structure-function relationships of bioactive molecules, monoclonal antibodies have proven to be excellent tools. In the present study, on the basis of epitope analysis using 19 different monoclonal antibodies against human TSH, the surface structure of this hormone was proposed in a two-dimensional map. The epitope map of TSH was useful for construction of available immunoassays for this hormone and its subunit, and to detect the abnormality in the structure of recombinant TSH. Further studies were attempted to assess the effects of monoclonal antibodies on the function of TSH. Consequently, our results suggest that the beta-subunit is indispensable for recognizing the receptor and that the alpha-subunit is required for signal transduction in postreceptor step(s). The applications of the present analysis are underway to detect the abnormalities in the structure and function of TSH in clinical specimens.
促甲状腺激素（TSH）是异源二聚体糖蛋白激素家族的一员，这些激素具有共同的α亚基，但激素特异性β亚基不同。迄今为止，已经进行了大量研究以阐明糖蛋白激素的结构-功能关系和激素作用的分子机制。另一方面，在临床样本中，特别是在恶性疾病中，已经观察到糖蛋白激素以及TSH在结构和功能上的几种异常情况。为了探究生物活性分子的结构-功能关系，单克隆抗体已被证明是出色的工具。在本研究中，基于使用19种针对人TSH的不同单克隆抗体进行的表位分析，在二维图谱中提出了该激素的表面结构。TSH的表位图有助于构建针对该激素及其亚基的有效免疫测定方法，并检测重组TSH结构中的异常情况。我们进一步尝试研究单克隆抗体对TSH功能的影响。因此，我们的结果表明，β亚基对于识别受体是必不可少的，而α亚基是受体后步骤信号转导所必需的。目前正在应用本分析方法检测临床标本中TSH结构和功能的异常情况。
