Figure 3.

Thyroid hormone action in bone cells. A, In hypothyroidism, despite maximum DIO2 (D2) and minimum DIO3 (D3) activities, TRα1 remains unliganded and bound to corepressor, thus inhibiting T₃-target gene transcription. B, In the euthyroid state, D2 and D3 activities are regulated to optimize ideal intracellular T₃ availability, resulting in displacement of corepressor and physiological transcriptional activity of TRα1. C, In thyrotoxicosis, despite maximum D3 and minimum D2 activities, supraphysiological intracellular T₃ concentrations result in increased TRα1 activation and enhanced T₃-target gene responses.