Part of “CHAPTER 31 – THYROID PHYSIOLOGY: HORMONE ACTION, RECEPTORS, AND POSTRECEPTOR EVENTS“

Many factors potentially can modulate TH-mediated transcription. These include variability among TR isoforms, TR complexes, heterodimerization partners, nature of TREs, and TR phosphorylation state.8,23a,23b These factors likely influence interactions of liganded TR with TR-associated nuclear proteins called coactivators. Several such proteins have been identified that interact with liganded TR and enhance TH-mediated transcriptional activation.11,12 A 160-kDa protein called steroid receptor coactivator-1 (SRC-1)25 has been identified that interacts with steroid-hormone receptors and TR. SRC-1 mRNA undergoes alternative splicing to generate multiple SRC-1 isoforms, although the functional significance of these SRC-1 isoforms currently is not known.26 Several other 160-kDa proteins also interact with liganded nuclear-hormone receptors and TRs, as well as share partial sequence homology with SRC-1. These findings suggest that a family of coactivators related to SRC-1 may exist.11,12 Some studies have suggested that interaction of coactivators with nuclear-hormone receptors involves the carboxy-terminal AF-2 subregion, although other subregions of the TR ligand-binding domain also may be involved.