Thyroid hormone receptor activity in the absence of ligand: Physiological and developmental implications

►Uliganded TRβ1 is involved in upregulation of TRH in hypothyroidism. ►Unliganded TRα controls some aspects of pre-metamorphosis. ►Unliganded TRα1 is involved in the timing of K+ channel expression in the cochlea. ►Apo- to holo-receptor switch influences gene expression during heart development. ►Induction of the Klf2 transcription factor in lung and pneumocyte I maturation requires unliganded TR.