Fig. 4.

Model for resistance to thyroid hormone in RTHβ patients. a In both normal and RTH patients, wild-type TRβ and TRα isoforms derived from normal THRB and THRA alleles bind as TR/RXR heterodimers to the TRE and are able to activate transcription. b The mutant TRβ encoded by the abnormal THRB allele in RTH patients bind to the TRE constitutively in both the presence and absence of T₃. Since it has decreased ligand-binding affinity, its ability to recruit co-activators and activate transcription is impaired. The unliganded mutant TR/RXR heterodimer thus competes with T₃-bound wild type TR/RXR heterodimer for binding to the TRE