Sakurai A, Takeda K, Ain K, Ceccarelli P, Nakai A, Seino S, Bell G I, Refetoff S, DeGroot L J
Thyroid Study Unit, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1989 Nov;86(22):8977-81. doi: 10.1073/pnas.86.22.8977.
The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine----cytosine replacement in the codon for amino acid 340 resulted in a glycine----arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor beta gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor beta gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.
全身性甲状腺激素抵抗综合征的特征是，在整体代谢正常的状态下循环甲状腺激素水平升高，且对三碘甲状腺原氨酸不能正常反应。我们评估了一个遗传性全身性甲状腺激素抵抗的家族，以检测其甲状腺激素核受体的异常情况。患者甲状腺激素核受体β基因的两个等位基因之一，其第340位密码子中的单个鸟嘌呤-胞嘧啶替换，导致激素结合域中的甘氨酸-精氨酸替换。该突变型人类甲状腺激素核受体β基因的体外翻译产物不能结合三碘甲状腺原氨酸。因此，全身性甲状腺激素抵抗可能是由异常甲状腺激素核受体分子的表达所致。
