Study on the mechanisms of receptor dysfunction with special reference to Basedow's disease

1. 利用人、猪和大鼠甲状腺细胞，用免疫细胞化学方法证实了自身免疫性甲状腺疾病患者自身抗体在甲状腺细胞膜上的结合位点。这些自身抗体包括TSAb、TBII和TSBAb型。根据细胞培养条件和系统的不同，抗原位点的定位模式不同，可分为弥漫性均匀型、病理分布型和局灶性细胞质过程型。2 .用山萝卜过氧化物酶标记的TSH和胶体金标记的TSH作为配体，在体外培养的甲状腺细胞上定位TSH受体位点。检测抗受体自身抗体TSAB、TBII和TSBAb对标记TSH与其受体结合的影响。结果表明，它们的抗体活性与自身抗体的结合抑制活性呈正相关，提示刺激活性或TSH结合抑制活性在形态学上是可以证明的。采用凝集素结合法和甲状腺过氧化物酶（TPO）和γ -谷氨酰转肽酶（GGT）的酶组织化学方法，研究了与TSH受体表达密切相关的甲状腺细胞膜的极性和功能。结果表明，RCA凝集素可作为甲状腺细胞膜腔面标记物，而tpo和GGT在甲状腺细胞膜上的表达呈负相关，前者可作为甲状腺功能分化的标记物，后者可作为甲状腺肿瘤发生的指示物。

1. The binding sites on the thyroid cell membrane of the autoantibodies from the patients of autommunoe thyroid diseases were immunocytochemically demonstrated, using the cultured cells of human, porcine and rat thyroid Glands. These autoantibodies included TSAb, TBII and TSBAb types. The pattern of localization of antigenic sites was variable, such as diffuse and homogeneous type, pathchy distribution type and focal cytoplasmic process type depending on the conditions and systems of cell culture.2. Horesradish peroxidase lablelled, and colloidal gold labelled TSH were successfully paalied as the ligands to localize the receptor site of TSH on the cultured thyroid cells.3. The effects of antireceptor autoantibodies, TSAB, TBII and TSBAb on the binding of the labelled TSH with its receptor were examined. The results showed that there was a positive correlation between their antibody activity and the binding inhibitory activity of autoantibodies, suggesting that the stimulatory activity or TSH binding inhibitory activity could be demonstrable morphologically.4. The polarity and function of thyroid cell membrane which are closely related with the expression of TSH receptor were investigated by the lectin binding method and enzyme histochemistry of thyroid peroxidase (TPO) and gamma-glutamyl transpeptidase (GGT). It was clarified that RCA lectin was useful as a marker of luminal surface of thyroid cell membrane, and that tpo and GGT were inverse in the expression on the thyroid cell membrane, the former as a marker of functional differentiation and the latter as an indicator of tumorigenesis in DIPH treated rat thyroid glands.