Thyroid hormone receptors in health and disease.

Thyroid hormones (TH) play a key role in energy homeostasis throughout life. Thyroid hormone production and secretion by the thyroid gland is regulated via the hypothalamus-pituitary-thyroid (HPT)-axis. Thyroid hormone has to be transported into the cell, where it can bind to the thyroid hormone receptor (TR) in the nucleus to exert its effect on cellular gene-transcription. Mutations in both the THRA and THRB gene have been described, each inducing a characteristic phenotype clearly showing the selective effect of an excess or shortage of thyroid hormone in specific TRα and TRβ regulated organs. Profound changes in thyroid hormone metabolism occur during a variety of non-thyroidal illnesses, each associated with reduced TR expression in a tissue-specific manner. However, thyroid hormone action at the tissue level during illness is not a simple reflection of the extent of TR expression as illness has additional differential effects on local thyroid hormone availability in various organs.