Messier N, Langlois M F
Department of Medicine, Division of Endocrinology and Dept. of Biochemistry, Faculty of Medicine, University of Sherbrooke, C.U.S.E. , Quebec, J1H 5N4, Sherbrooke, Canada.
Mol Cell Endocrinol. 2000 Jul 25;165(1-2):57-66. doi: 10.1016/s0303-7207(00)00266-5.
3,5,3'-triiodothyroacetic acid (Triac) is a naturally occurring triiodothyronine (T(3)) analog, which has been used on an empirical basis to treat the syndrome of resistance to thyroid hormone (RTH). The aim of our studies was to compare the effects of Triac and T(3) on negative and positive thyroid hormone response elements (TREs). We used transient transfections with luciferase reporter genes to show that on palindromic, inverted palindrome and human TRH reporters, Triac is more potent than T(3) for transcriptional regulation by TRbeta1 and TRbeta2 isoforms, while regulation by TRalpha1 is equivalent for both ligands. Other TREs (direct repeat, hTSHalpha and hTSHbeta) are not regulated differently by Triac and T(3). Dose-response curves show that the difference between Triac and T(3) is maximal in the 1-10 nM range. Receptor-binding studies reveal a greater affinity of Triac than T(3) for TRbeta1 and TRbeta2 isoforms, which could explain its isoform-specific effects. These data suggest that the TRE- and TR isoform-specific effects of Triac favor its use in RTH.
3,5,3'-三碘甲状腺乙酸（Triac）是一种天然存在的三碘甲状腺原氨酸（T(3)）类似物，已凭经验用于治疗甲状腺激素抵抗综合征（RTH）。我们研究的目的是比较Triac和T(3)对甲状腺激素阴性和阳性反应元件（TREs）的影响。我们使用荧光素酶报告基因进行瞬时转染，结果表明，在回文、反向回文和人促甲状腺激素释放激素（TRH）报告基因上，对于TRβ1和TRβ2亚型的转录调控，Triac比T(3)更有效，而TRα1对两种配体的调控作用相当。其他TREs（直接重复序列、人促甲状腺激素α亚基和人促甲状腺激素β亚基）受Triac和T(3)的调控无差异。剂量反应曲线表明，Triac和T(3)之间的差异在1 - 10 nM范围内最大。受体结合研究显示，Triac对TRβ1和TRβ2亚型的亲和力高于T(3)，这可以解释其亚型特异性效应。这些数据表明，Triac对TREs和TR亚型的特异性效应有利于其在RTH中的应用。
