Thyroid Hormone Metabolism

Abstract

Thyroid hormone (TH) metabolism comprises all biochemical reactions of TH and iodothyronines, which are catalyzed by various classes of enzymes of the vertebrate organism and its gastrointestinal microbiota. These enzymes alter the biochemical properties of the TH thyroxine (T4) and 3,3′,5-triiodothyronine (T3), both of which are secreted by the thyroid gland, and modify the properties of TH metabolites (THM) derived from T4 and T3. Metabolism by the three deiodinase (DIO) selenoenzymes leads to either activation or inactivation of TH. Metabolism by glucuronidases, sulfotransferases, or sulfatases, changes the solubility, distribution, and biological potency of these hydrophobic THM. Enzymes metabolizing the amino acid side chain (decarboxylases and monoamine oxidases) of THM generate further iodinated metabolites, which may exert actions either related to that of the thyromimetic hormone T3 or presenting with a new spectrum of actions (thyronamines and thyroacetic acids). Oxidative reactions in activated macrophages and neutrophils cleave the diphenylether bridge of THM and destroy hormonal activities but liberate reactive iodine species. TH metabolism allows cell-type-specific fine-tuning of TH action at the tissue, cellular, and subcellular level by controlling the local availability of the active TH T3.Target cells of THM action thus become to some extent independent of systemic T4 and T3 supplied by the thyroid gland and the circulating blood concentration. Deiodinase activities in the hypothalamic TRH neurons and the pituitary thyrotrope cells control the negative feedback regulation of TH on thyrotropin releasing hormone (TRH) and thyrotropin (TSH) synthesis and secretion.