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

The transcriptional activity of the thyroid hormone receptors is modulated by the ligand, T3, but they have also activity as aporeceptors, in the unliganded state. Aporeceptor activity is thought to contribute to the severity of profound hypothyroidism. During development thyroid hormone receptors are expressed before onset of thyroid gland function and are present therefore in many tissues mainly as aporeceptors. The question we address is whether thyroid hormone aporeceptors are involved in physiological and/or developmental processes.

The scope of this article is to review the evidence for a role of thyroid hormone aporeceptors in physiology and development. Related to this topic is the activity of mutant receptors unable to bind hormone. These receptors usually have dominant negative activity. This review focuses on the wild type receptors, and does not discuss the properties of mutant receptors.

Unliganded thyroid hormone receptors influence the timing and control certain aspects of amphibian pre-metamorphosis. In mammals they are likely to influence maturational processes in the brain and other organs before onset of thyroid gland function. Expression of types 2 and 3 deiodinases which control the local tissue concentration of T3 regulates the fractional receptor occupancy and therefore the relative proportion of aporeceptors. This article is part of a Special Issue entitled Thyroid hormone signalling.