Thyroid hormone receptors and type I iodothryronine 5′-deiodinase activity of human thyroid adenomas and benign cold nodules
Thyroid hormone receptors and type I iodothryronine 5′-deiodinase activity of human thyroid adenomas and benign cold nodules
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DOI：
10.1055/s-2002-32147
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发表时间：
2002-06-01
影响因子：
1.8
通讯作者：
Köhrle, J
中科院分区：
文献类型：
--
作者：
Brtko, J;Bobálová, J;Köhrle, J
大多数甲状腺腺瘤是克隆起源的。在一部分毒性腺瘤和冷结节中，促甲状腺激素受体或G（s）-α基因的激活突变可能解释了这些良性肿瘤功能的改变。本研究旨在研究人类毒性腺瘤和冷结节中功能性甲状腺激素受体（主要甲状腺激素信号介质）的状态，并与同一患者的正常甲状腺组织进行比较。使用人I型碘甲腺原氨酸5 '-脱碘酶的甲状腺激素反应元件（TRE）DR 4（“直接重复”4）的电泳迁移率变化测定证明了甲状腺组织核提取物中甲状腺激素受体（TRs）的DNA结合。与正常甲状腺组织相比，TA中TRs与DR 4甲状腺激素反应元件的功能结合特性显著增加（p < 0.05）。相反，与正常甲状腺组织相比，氯化萘中TR-TRE复合物的形成明显减少。此外，还分析了良性肿瘤、甲状腺TA和氯化萘中碘甲腺原氨酸5 '-脱碘酶（5' DI）的功能活性，并与正常甲状腺组织进行了比较。与正常组织相比，TA中5 'DI活性显著增高（p < 0.01），CN中5' DI活性降低，提示甲状腺良性肿瘤中TR-TRE复合物形成状态和5 'DI活性均发生改变。
The majority of thyroid adenomas are of clonal origin. In a subset of toxic adenomas (TAs) and cold nodules (CNs) activating mutations in the thyrotropin (TSH) receptor or G(s)-alpha gene may explain the altered functions in these benign tumours, The present study was undertaken to investigate the status of functional thyroid hormone receptors, major thyroid hormone signal mediators, in both the human TAs and CNs in comparison with a normal thyroid tissue from the same patient. Electrophoretic mobility shift assays using a DR4 ("direct repeats" 4), a thyroid hormone responsive element (TRE) of human type I iodothyronine 5'-deiodinase demonstrated the DNA-binding of thyroid hormone receptors (TRs) in thyroid tissue nuclear extracts. A significant increase (p < 0.05) in the functional binding properties of TRs to the DR4 thyroid hormone responsive element was found in TAs when compared to normal thyroid tissue. Contrary, a marked diminution in the TR-TRE complex formation was found in CNs in comparison with normal thyroid tissue. In addition, functional activity of the iodothyronine 5'-deiodinase (5'DI) was analyzed in benign tumours, thyroid TAs and CNs in comparison with that of normal thyroid tissue. A significantly increased (p < 0.01) activity of 5'DI was demonstrated in TAs, and in contrast, decreased Values of the enzyme activity were found in CNs when compared to a normal tissue.From the data it is suggested that both the Status of TR-TRE complex formation and the activity of the 5 DI may be altered in benign tumours of human thyroid gland.