Immunohistochemical demonstration of thyrotropin (TSH) -receptor in normal and diseased human thyroid tissues using monoclonal antibody against recombinant human TSH-receptor protein.

TSH受体在控制甲状腺功能和增殖中起关键作用。为了证明该受体在正常和患病的人甲状腺组织中，我们使用针对重组人TSH受体蛋白的单克隆抗体（T3-356）进行免疫组织化学分析，该抗体识别人TSH受体604-764位片段内的表位在正常人甲状腺组织中，仅沿着扁平滤泡细胞的基底细胞表面观察到阳性染色。在腺瘤性结节、腺瘤和乳头状癌的组织中，沿着滤泡细胞的基底细胞表面也发现阳性染色，此外，还观察到相当多的胞浆染色。滤泡细胞的顶面和侧面细胞表面无染色。在乳头状癌和滤泡性腺瘤中染色强度较强，而在嗜酸性细胞腺瘤中染色强度较弱 关于我们 与正常甲状腺组织相比，AS和腺瘤性结节。乳头状癌、未分化癌和髓样癌的鳞状上皮化生灶未见阳性染色。这些结果表明，在肿瘤状态下，TSH受体基本上保留在甲状腺滤泡细胞的基底细胞表面。3例Graves病患者术前用抗甲状腺药物治疗，但手术时仍有甲亢。在Graves甲状腺滤泡细胞的基底细胞表面也观察到沿着阳性染色。与正常甲状腺相比，Graves甲状腺的染色强度显著增加。在Graves甲状腺的柱状滤泡细胞的乳头状突起灶中观察到最强的染色。这一免疫组化结果表明，TSH受体的数量在Graves甲状腺中增加，尽管存在刺激型抗TSH受体自身抗体持续刺激甲状腺滤泡细胞，但Graves甲状腺中可能不存在TSH受体的下调机制。这些发现可能解释了刺激型自身抗体是如何能够作为一个刺激剂，并保持增加甲状腺激素的生产在Graves' disease.Further调查使用Western印迹和原位杂交的TSH受体蛋白的定量分析。少

The TSH-receptor plays a key role in the control of thyroid function and proliferation. To demonstrate this receptor in normal and diseased human thyroid tissues, we performed an immunohistochemical analysis using a monoclonal antibody (T3-356) against recombinant human TSH receptor protein, which recognizes an epitope within the fragment in position 604-764 of human TSH-receptor (C-terminal region) .In normal human thyroid tissues, a positive staining was observed exclusively along the basal cell surface of the flattened follicular cells. In the tissues from adenomatous nodules, adenomas and papillary carcinomas, a positive staining was also found along basal cell surface of the follicular cells, and in addition, a considerable cytoplasmic staining was also observed. Apical and lateral cell surface of the follicular cells showed no staining. The staining intensity was more intense in the papillary carcinomas and follicular adenomas, and it was less intense in the oxyphilic cell adenom … More as and adenomatous nodules compared with the normal thyroid tissues. The foci of squamous cell metaplasia of papillary carcinomas, anaplastic carcinoma and medullary carcinoma did not show a positive staining. These findings indicate that TSH-receptor is preserved essentially in the basal cell surface of the thyroid follicular cells in neoplastic conditionsThree cases of Graves' disease had been preoperatively treated with anti-thyroid drugs, but were still hyperthyroid at surgery. The positive staining was also observed along the basal cell surface of the follicular cells from Graves' thyroids. The staining intensity was significantly increased in the Graves' thyroids compared with the normal thyroids. The most intense staining was noted in the foci of papillary projection of the columnar follicular cells of the Graves' thyroids. This immunohistochemical finding suggested that the number of TSH-receptors was increased in Graves' thyroids and that a down-regulatory mechanism of TSH-receptor may not be present in Graves' thyroids despite of the continuous stimulation of the thyroid follicular cells by the presence of stimulatory-type autoantibodies against TSH-receptor. Such findings may explain how stimulatory-type autoantibodies are able to act as a stimulator and maintain increased thyroid hormone production in Graves' disease.Further investigation using western blotting and in situ hybridization for quantitative analysis of TSH-receptor protein is performed. Less