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

1.用人、猪和大鼠甲状腺培养细胞，对自身免疫性甲状腺疾病患者的自身抗体在甲状腺细胞膜上的结合位点进行了免疫细胞化学显示。这些自身抗体包括TSAb、TBII和TSBAb型。抗原位点的定位方式因细胞培养条件和系统的不同而不同，可分为弥漫均匀型、病理性分布型和灶性胞质突起型.辣根过氧化物酶标记和胶体金标记的TSH作为配体成功地定位了培养的甲状腺细胞上TSH的受体位点.本文研究了抗受体自身抗体TSAB、TBII和TSBAb对标记TSH与其受体结合的影响。结果表明，自身抗体的抗体活性与其结合抑制活性之间存在正相关，提示其刺激活性或TSH结合抑制活性可通过形态学表现出来.应用凝集素结合法和甲状腺过氧化物酶（TPO）、γ-谷氨酰转肽酶（GGT）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。在DIPH处理的大鼠甲状腺中，RCA凝集素可用作甲状腺细胞膜腔表面的标记物，而TPO和GGT在甲状腺细胞膜上的表达是相反的，前者作为功能分化的标记物，后者作为肿瘤发生的指示物。

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.