Deiodinases

implications of the local control of thyroid hormone action

Bianco, Antonio C.
Kim, Brian W.

Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Address correspondence to: Antonio C. Bianco, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 77 Avenue Louis Pasteur, HIM Building, Room 643, Boston, Massachusetts 02115, USA. Phone: (617) 525-5153; Fax: (617) 731-4718; E-mail: [email protected].

Nonstandard abbreviations used: D1, type I iodothyronine deiodinase; Dio3, type IIIiodothyronine deiodinase; D1KO mice, Dio1-knockout mice; GPBAR1, G protein-coupled bile acid receptor 1; PTU, propylthiouracil; T3, 3,5,3′-triiodothyronine; T4, thyroxine; TR, thyroid hormone receptor; TRH, TSH-releasing hormone; TSH, thyroid-stimulating hormone; UCP-1, uncoupling protein 1; VDU, von Hippel-Lindau protein-interacting deubiquitinating enzyme; WSB-1, WD repeat and SOCS box-containing 1.

Conflict of interest: The authors have declared that no conflict of interest exists.

Journal of Clinical Investigation 116(10):p 2571-2579, October 2006.

The deiodinases activate or inactivate thyroid hormone, and their importance in thyroid hormone homeostasis has become increasingly clear with the availability of deiodinase-deficient animals. At the same time, heightened interest in the field has been generated following the discovery that the type 2 deiodinase can be an important component in both the Hedgehog signaling pathway and the G protein–coupled bile acid receptor 1–mediated (GPBAR1-mediated) signaling cascade. The discovery of these new roles for the deiodinases indicates that tissue-specific deiodination plays a much broader role than once thought, extending into the realms of developmental biology and metabolism.