Mechanism of thyroid hormone receptor action. The thyroid hormone receptor (TR) and retinoid X receptor (RXR) form heterodimers that bind specifically to thyroid hormone response elements (TRE) in the promoter regions of target genes. In the absence of hormone, TR binds co-repressor (CoR) proteins that silence gene expression. The numbers refer to a series of ordered reactions that occur in response to thyroid hormone: (1) T₄ or T₃ enters the nucleus; (2) T₃ binding dissociates CoR from TR; (3) Coactivators (CoA) are recruited to the T₃-bound receptor; (4) gene expression is altered.