Thyroid hormone deiodinases: physiology and clinical disorders

Thyroid hormone action is achieved through the binding of 3,5,3'-triiodothyronine to its nuclear receptor, which results in alterations in gene expression. An impairment in thyroid hormone action during vertebrate development results in severe, irreversible abnormalities in tissue growth, maturation, and function. The deiodinases are a family of selenoproteins expressed in a number of fetal and adult tissues that catalyze the activation and inactivation of thyroid hormones. Their unique biochemical characteristics and tissue and developmental expression patterns suggest that deiodinases may control the concentration of active thyroid hormone available to specific tissues or cell types at certain stages of development. The deiodinases thus appear to play an important role in regulating thyroid hormone action at a prereceptor level. Current research focusing on a better understanding of the biochemistry, regulation, and physiologic role of these enzymes is the focus of this review.