Role of the Iodothyronine Deiodinases in the Physiology and Pathophysiology of Thyroid Hormone Action

Thyroxine (T4) is a prohormone and must be activated to 3,5,3 -triiodothyronine (T3) by either type 1 (D1) or type 2 (D2) selenodeiodinase. A third deiodinase (D3) inactivates T3 or T4 by removal of an inner ring iodine. These reactions require both a deiodinase enzyme and a cofactor, probably a thiol, to reduce the oxidized selenolyl group in the active center of each deiodinase. Thus, deiodination rates depend on both the enzyme and cofactor. The source of most of the circulating T3 is D1-mediated, while D2 provides nuclear receptor-bound hormone. Using sensitive and specific assays, it has become apparent that both D2 and D3 are widespread throughout vertebrate tissues. The complex interactions between the activating D2 and the inactivating D3 in tissues expressing these two enzymes determine the intracellular T3 concentration. This provides enormous flexibility for both developmental and tissue regeneration processes, allowing exquisite control of intracellular T3 concentrations. The endogenous factors regulating the activity of these enzymes, Received: August 27, 2012 Accepted after revision: October 4, 2012 Published online: November 9, 2012 Dr. P. Reed Larsen Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School Harvard Institutes of Medicine, Room 644 77 Avenue Louis Pasteur, Boston, MA 02115-5727 (USA) E-Mail plarsen @ partners.org © 2012 European Thyroid Association Published by S. Karger AG, Basel 2235–0640/12/0014–0232$38.00/0 Accessible online at: www.karger.com/etj D ow nl oa de d by : 54 .7 0. 40 .1 1 10 /6 /2 01 7 10 :2 5: 43 A M