Hetero- and homodimeric receptors in thyroid hormone and vitamin A action

Abstract

Understanding of the complex responses to thyroid and retinoid hormones has been greatly advanced through the cloning of specific nuclear receptors. The receptors belong to a large family of intracellular proteins that include the steroid hormone receptors and many "orphan" receptors for which no specific ligands are known. Recent studies on the mechanisms of actions of thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) has revealed a complex system of receptor interactions. In contrast to the steroid hormone receptors that function predominantly as homodimers, TRs and RARs require heterodimer formation with the retinoid X receptors (RXR) for efficient DNA binding and transcriptional activation. RXRs in addition can form homodimers in the presence of specific ligands such as 9-cis retinoic acid. RXR homodimers recognize a subset of retinoic acid responsive elements (RARE). The COUP-TF orphan receptors also bind certain RAREs as homodimers and can inhibit thereby RAR/RXR heterodimers as well as RXR homodimer activities. Thus, a complex network of receptor interaction has been unraveled that promises a better understanding of thyroid and retinoid hormone action and that may allow the design of more effective hormonal therapeutics.