Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions

Abstract

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.

Insights on the Association between Thyroid Diseases and Colorectal Cancer

“…As above mentioned, the biological activity of THs is mainly determined by the intracellular levels of deiodinases that catalyze the production (D1 and D2) or degradation (D3) of T 3 [ 101 ]. In several human cancers, a dysregulation of deiodinases expression is frequently encountered, and affects the intracellular TH actions [ 102 , 103 , 104 , 105 ].…”

Thyroid hormone Beta receptor agonists for treatment of kidney disease: A promising agent?

“…16,17 D1 is responsible from the large proportion of T4 to T3 conversion and mainly expressed at the cellular membrane of thyroid tissue, liver and kidney cells. 18 D2 is mainly expressed at the endoplasmic reticulum of central nervous system including the pituitary gland, muscle tissue and brown adipose tissue cells while D3 is mainly expressed in pancreatic beta cells, central nervous system and foetal tissues including placenta and pregnant uterus. [19][20][21] Another important aspect of D3 is the selective upregulation during critical illnesses.…”

“…D1 has three‐times less affinity towards T4 compared with other deiodinases while its primary substrate is reverse T3 as shown by studies illustrating elevated levels of serum reverse T3 in animal subjects with loss‐of‐function mutation at D1 16,17 . D1 is responsible from the large proportion of T4 to T3 conversion and mainly expressed at the cellular membrane of thyroid tissue, liver and kidney cells 18 . D2 is mainly expressed at the endoplasmic reticulum of central nervous system including the pituitary gland, muscle tissue and brown adipose tissue cells while D3 is mainly expressed in pancreatic beta cells, central nervous system and foetal tissues including placenta and pregnant uterus 19–21 .…”

Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication

“…DIO1 and DIO2 catalyze the conversion of the inactive thyroid hormone T4 to the active T3 form through the removal of an iodine atom. DIO3 carries out the deactivation of thyroid hormone by either reducing T4 into the inactive reverse T3 (rT3), or by converting T3 to T2 [ 58 ]. SEPHS2 is unique in that it directly partakes in selenium metabolism by helping to synthesize selenophosphate, which provides the selenium used to make Sec-loaded TRSP for selenoprotein translation [ 59 ].…”