Triac regulation of transcription is T-3 receptor isoform- and response element-specific

3,5,3'-triiodothyroacetic acid (Triac) is a naturally occurring triiodothyr onine (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 h ormone response elements (TREs). We used transient transfections with lucif erase reporter genes to show that on palindromic, inverted palindrome and h uman TRH reporters, Triac is more potent than T-3 for transcriptional regul ation by TR beta 1 and TR beta 2 isoforms, while regulation by TR alpha 1 i s equivalent for both ligands. Other TREs (direct repeat, hTSH alpha and hT SH beta) are not regulated differently by Triac and T-3. Dose-response curv es 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 TR beta 1 and TR beta 2 isoforms, which could explain its isoform-spe cific effects. These data suggest that the TRE- and TR isoform-specific eff ects of Triac favor its use in RTH. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.