Triiodothyronine (T3) differentially affects T3-receptor/retinoic acid receptor and T3-receptor/retinoid X receptor heterodimer binding to DNA.

Thyroid hormone receptor (TR) heterodimerizes with retinoic acid receptor (RAR), retinoid X receptor (RXR), and triiodothyronine receptor auxiliary protein (TRAP) on natural and synthetic hormone response elements. Recently we showed that triiodothyronine (T3) decreased TR homodimer, but not TR/TRAP heterodimer, binding to several thyroid hormone response elements (TREs). The effect of ligand on TR/RAR and TR/RXR heterodimer binding to DNA is not known. In this study, we showed that TR formed heterodimers with RAR and RXR on a retinoic acid (RA) response element and two TREs. Surprisingly, T3, but not RA, decreased TR/RAR heterodimer binding to DNA. In contrast, T3, all-trans-RA, or 9-cis-RA did not affect TR/RXR binding to DNA. This finding suggests that TR/RXR heterodimer is a stable receptor complex that remains bound to response elements in the presence of ligand and therefore may be a receptor complex involved in T3-regulated transcription.