In the absence of hormone, TR in complex with corepressor proteins bind to HREs in a transcriptionally inactive state. Binding of thyroid hormone results in a conformational change in TR which displaces corepressor from the receptor/DNA complex and recruitment of coactivator proteins. The DNA/TR/coactivator complex then recruits RNA polymerase that transcribes downstream DNA into messenger RNA and eventually protein that results in a change in cell function.
There are three forms of the thyroid hormone receptor designated alpha-1, beta-1 and beta-2 that are able to bind thyroid hormone. There are two TR-α receptor splice variants encoded by the THRA gene and two TR-β isoform splice variants encoded by the THRB gene:
TR-α1 (widely expressed and especially high expression in cardiac and skeletal muscles)
TR-α2 (homologous with viral oncogene c-erb-A, also widely expressed but unable to bind hormone)
TR-β1 (predominately expressed in brain, liver and kidney)
TR-β2 (expression primarily limited to the hypothalamus and pituitary)