Thyroid hormone receptor [alpha] is a molecular switch of cardiac function between fetal and postnatal life

Thyroid hormones are involved in the regulation of many physiological processes and regulate gene transcription by binding to their nuclear receptors TR[alpha] and TR[beta]. In the absence of triiodothyronine (T3), the unliganded receptors (aporeceptors) do bind DNA and repress the transcription of target genes. The role of thyroid hormone aporeceptors as repressors was observed in hypothyroid adult mice, but its physiological relevance in nonpathological hypothyroid conditions remained to be determined. Here we show that, in the normal mouse fetus, TR[alpha] aporeceptors repress heart rate as well as the expression of TR[beta] and several genes encoding ion channels involved in cardiac contractile activity. Right after birth, when T3 concentration sharply increases, liganded TR[alpha] (holoreceptors) turn on the expression of some of these same genes concomitantly with heart rate increase. These data describe a physiological situation under which conversion of TR[alpha] from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process.