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 TR alpha and TR beta 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