Thyroxine 5-deiodinase (DIO3)

Thyroxine 5-deiodinase (DIO3) is a membrane-bound selenoenzyme that inactivates thyroid hormones by removing an iodine atom from the inner ring of thyroxine (T4) and triiodothyronine (T3), generating reverse T3 (rT3) and 3,3′-diiodothyronine (T2) respectively[2][3][5][6]. This regulation is essential for controlling local and systemic thyroid hormone levels,particularly during embryogenesis and in the placenta, protecting developing tissues from premature thyroid hormone action[2][3][5]. DIO3-deficient mice show developmental, neurological, auditory, and reproductive deficits; excess DIO3 in certain tumors can cause consumptive hypothyroidism[3][5]. DIO3 contains a selenocysteine residue encoded by a specialized UGA codon and localizes mainly in fetal and neonatal tissues, placenta, and select adult tissues[2][5][8]. It is an imprinted gene, crucial for proper maternal-fetal thyroid hormone transport and local tissue homeostasis[2][5][8].

Other names

Type 3 iodothyronine deiodinaseD35DIIIDIOIIITXDI3iodothyronine type III deiodinase5-deiodinase type IIItype III iodothyronine selenodeiodinaseselenoprotein DIO3thyroxine deiodinase type III (selenoprotein)deiodinase iodothyronine, placental typeITDI3

Inhibition would elevate local active thyroid hormones by reducing inner-ring deiodination/inactivation. Modulation affects tissue exposure to T3 and T4, especially important during development.