Iodothyronine deiodinase type 3 (DIO3) (DIO3)

Iodothyronine deiodinase type 3 (DIO3) is a critical selenoprotein enzyme responsible for the inactivation of thyroid hormones through inner-ring deiodination. It converts thyroxine (T4) into reverse triiodothyronine (rT3) and triiodothyronine (T3) into 3,3'-diiodothyronine (T2), both of which are biologically inactive (UniProt P55073). This enzyme is highly expressed during fetal development, particularly in the placenta and fetal tissues, where it serves to protect the developing organism from excessive maternal thyroid hormone levels (PubMed: 25942361). In adults, DIO3 expression is typically restricted but can be pathologically upregulated in conditions such as large infantile hemangiomas, leading to a severe form of "consumptive hypothyroidism" (PubMed: 10965100). Furthermore, DIO3 is often overexpressed in various cancers and during critical illness, contributing to the "low T3 syndrome" by accelerating the clearance of active thyroid hormones (PubMed: 29432821). While specific clinical drugs targeting DIO3 are limited, it is known to be inhibited by compounds like iopanoic acid and gold thioglucose, and its activity is dependent on adequate selenium levels (PubChem). Understanding the regulation of DIO3 is essential for managing thyroid homeostasis in patients with non-thyroidal illness or deiodinase-producing tumors.

Other names

Type 3 iodothyronine deiodinaseType III 5-deiodinaseITDI3TXDI3D3

Inhibitors of DIO3 block the inner-ring deiodination of thyroxine (T4) and triiodothyronine (T3), preventing their conversion into the inactive metabolites reverse T3 (rT3) and 3,3'-diiodothyronine (T2).