Coordinated regulation of and transcriptional activation by Xenopus thyroid hormone and retinoid X receptors.

Thyroid hormone (T3) plays a causative role in amphibian metamorphosis. This regulation is thought to be mediated by heterodimers of T3 receptors (TRs) and retinoid X receptors (RXRs). We report here that Xenopus TRs can indeed form strong heterodimers with Xenopus RXRs on the T3 response element (TRE) present in Xenopus TR beta genes. Using a T3-responsive in vivo transcription system established by introducing TRs and RXRs into Xenopus oocytes, we demonstrated that TR-RXR heterodimers repressed TR beta gene promoter in the absence of T3 and activated the promoter in the presence of the hormone. Furthermore, by analyzing the expression of TR and RXR genes, we showed that TR and RXR genes were coordinately regulated in different tissues during metamorphosis. Thus high levels of their mRNAs are present in the limb during early stages of limb development when morphogenesis occurs and in the tail toward the end of metamorphosis when it is being resorbed. Such correlations coupled with our TRE-binding and in vivo transcriptional activation experiments provide strong evidence that TRs and RXRs function together to mediate the effects of T3 during metamorphosis. These results further suggest a possible molecular basis for the temporal regulation of tissue-specific metamorphosis.