Internal medicine

Cell

Triiodothyronine

Deiodinase

Thyroid

Biology

Endocrinology

DIO2

Chemistry

Iodothyronine deiodinase

Thyroid hormones

Cell biology

Biochemistry

Homeostasis

Hormone

Medicine

Endocrinology and Metabolism

Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified—namely iodothyronine deiodinase 1 (DIO1), DIO2, and DIO3—that differ in their catalytic properties and tissue distribution. The deiodinases represent a dynamic system that changes in the different stages of life according to their functions and roles in various cell types and tissues. Deiodinase activity at the tissue level permits cell-targeted fine regulation of TH homeostasis, mediating the activation (DIO1 and DIO2) and inactivation (DIO3) of THs. Deiodinase homeostasis is the driving force that leads T3-target cells towards customized TH signaling, which takes into account both the hormonal circulating levels and the tissue-specific response. This review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.

Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions