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Endocrine Reviews 23 (1): 38-89
Copyright © 2002 by The Endocrine Society

Biochemistry, Cellular and Molecular Biology, and Physiological Roles of the Iodothyronine Selenodeiodinases

Antonio C. Bianco, Domenico Salvatore, Balázs Gereben, Marla J. Berry and P. Reed Larsen

Thyroid Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (A.C.B., M.J.B., P.R.L.), Boston, Massachusetts 02115; Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Universita’ Federico II (D.S.), 80131 Naples, Italy; Institute of Experimental Medicine, Hungarian Academy of Sciences (B.G.), Budapest, H-1083 Hungary

Correspondence: Address all correspondence and requests for reprints to: P. Reed Larsen, M.D., Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine Building, Room 550, Boston, Massachusetts 02115. E-mail: rlarsen{at}rics.bwh.harvard.edu

The goal of this review is to place the exciting advances that have occurred in our understanding of the molecular biology of the types 1, 2, and 3 (D1, D2, and D3, respectively) iodothyronine deiodinases into a biochemical and physiological context. We review new data regarding the mechanism of selenoprotein synthesis, the molecular and cellular biological properties of the individual deiodinases, including gene structure, mRNA and protein characteristics, tissue distribution, subcellular localization and topology, enzymatic properties, structure-activity relationships, and regulation of synthesis, inactivation, and degradation. These provide the background for a discussion of their role in thyroid physiology in humans and other vertebrates, including evidence that D2 plays a significant role in human plasma T3 production. We discuss the pathological role of D3 overexpression causing "consumptive hypothyroidism" as well as our current understanding of the pathophysiology of iodothyronine deiodination during illness and amiodarone therapy. Finally, we review the new insights from analysis of mice with targeted disruption of the Dio2 gene and overexpression of D2 in the myocardium.




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A. E. Balazs, I. Athanassaki, S. K. Gunn, N. Tatevian, S. A. Huang, M. W. Haymond, and L. P. Karaviti
Rapid Resolution of Consumptive Hypothyroidism in a Child with Hepatic Hemangioendothelioma Following Liver Transplantation
Ann. Clin. Lab. Sci., January 1, 2007; 37(3): 280 - 284.
[Abstract] [Full Text] [PDF]

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