Regulation of retinoid and thyroid hormone action through homodimeric and heterodimeric receptors

Biologic responses to retinoids and thyroid hormones are mediated by their intracellular receptor proteins. Many exciting advances have been made recently in understanding the molecular mechanism by which these receptor proteins operate. In contrast to the steroid hormone receptors that function predominantly as homodimers, thyroid hormone receptors (TRs)and retinoic acid receptors (RARs) require interaction with the retinoid X receptors (RXRs) for efficient DNA binding and transactivation. In addition, RXRs, in the presence of their specific ligands such as 9-cis RA, can form homodimers that recognize a subset of retinoic acid responsive elements (RAREs). The retinoid responses mediated by RXR homodimers and RAR-RXR heterodimers can be restricted by the COUP-TF orphan receptors that bind strongly to certain RAREs as homodimers. Thus, a complex network of receptor interaction has been unraveled that promises a better understanding of thyroid and retinoid hormone regulation of fundamental biologic processes and diseases.