Pathways of thyroid hormone metabolism

T4 is the main product secreted by the thyroid follicular cells and is regarded as a precursor of the bioactive hormone T3, most of which is produced by outer ring deiodination of T4 in peripheral tissues. Both T4 and T3 are inactivated by inner ring deiodination. Three deiodinases have been identified with outer and/or inner ring deiodinase activities, which play an important role in the tissue-specific regulation of thyroid hormone bioactivity. All three enzymes have recently been shown to contain selenocysteine residues. The second important pathway of thyroid hormone metabolism involves the conjugation of the phenolic hydroxyl group with sulfate or glucuronic acid. The glucuronides are excreted in bile, acting as intermediates in the enterohepatic cycle and fecal excretion of thyroid hormone. Sulfation accelerates the deiodination of different iodothyronines by the type I deiodinase and, thus, initiates the irreversible degradation of the hormone. If type I deiodinases activity is low, e.g. in the fetus, T3 sulfate may function as a reservoir from which active T3 is recovered by tissue sulfatase activity.