Type 3 iodothyronine deiodinase (DIO3)

Type 3 iodothyronine deiodinase (DIO3) is a selenium-containing enzyme that serves as the primary physiological inactivator of thyroid hormones by catalyzing the removal of an inner-ring iodine atom (UniProt, Wikipedia). It converts the prohormone thyroxine (T4) into reverse triiodothyronine (rT3) and the active hormone triiodothyronine (T3) into 3,3'-diiodothyronine (T2), both of which are metabolically inactive (NIH, Frontiers in Endocrinology). DIO3 is highly expressed during fetal development to protect developing tissues from excessive maternal thyroid hormone levels and remains active in the adult brain, skin, and placenta (NIH, e-enm.org). Pathological overexpression of DIO3 is associated with consumptive hypothyroidism, a condition where large tumors rapidly degrade circulating thyroid hormones, and it is also considered an oncofetal protein that promotes tumor cell proliferation in various cancers (Oncogene, NIH). Additionally, elevated DIO3 activity in the brain has been linked to major depressive disorder, suggesting that its inhibition could enhance antidepressant efficacy by increasing local T3 availability (PubMed, NIH). Current pharmacological research focuses on developing selective small-molecule inhibitors, such as dibromomaleic anhydride derivatives, to modulate thyroid hormone signaling in specific disease contexts, although achieving tissue specificity remains a significant therapeutic challenge (Oncogene, Wikipedia).

Other names

Iodothyronine deiodinase type 3Type III thyroxine 5-deiodinase5-deiodinaseD3DIOIII5DIIITXDI3Iodothyronine deiodinase type III

Inhibition of the inner-ring deiodination of thyroxine (T4) and triiodothyronine (T3) to prevent their conversion into inactive metabolites (rT3 and T2), thereby increasing local active thyroid hormone concentrations or suppressing tumor growth.