[Thyroid hormone metabolism and action]

Reductive deiodination of thyroid hormones at the phenolic and tyrosyl ring leads to the activation or inactivation of the thyromimetic activity inherent to thyroid hormones. Alterations in the activities of the three selenocysteine-containing enzymes, the iodothyronine deiodinases, have been reported during development and in specific cells and tissues of the adult organism. Furthermore, pathophysiological changes in the deiodinase expression lead to therapeutically relevant disturbances of the homeostasis of thyroid hormones. Metabolisation of thyroid hormones by conjugation of their phenolic 4'-OH group, their alanine side chain or cleavage of their diphenylether bridge also contributes to both local and systemic supply of thyromimetic activity or hormone degradation. Further components mediating the pleiotropic action of thyroid hormones in part include redundant T3 receptors, binding and transport proteins, metabolising enzymes and T3-regulated gene products. This is achieved in a finely tuned manner with multiple feedback control, malfunction or complete failure of individual components and networks involved in the iodothyronine metabolism and thyroid hormone action can thus be compensated or prevented.