ACTIVATION AND INACTIVATION OF THYROID-HORMONE BY TYPE-I IODOTHYRONINE DEIODINASE

The prohormone thyroxine (T4) is activated by outer ring deiodination (ORD) to 3,3',5-triiodothyronine (T3) and both hormones are degraded b y inner ring deiodination (IRD) to 3,3',5'-triiodothyronine (rT3) and 3,3'-diiodothyronine, respectively. Indirect evidence suggests that th e type I iodothyronine deiodinase (ID-I) in liver has both ORD and IRD activities, with preference for rT3 and sulfated iodothyronines as su bstrates. To establish this, we have compared the ORD of rT3 and IRD o f T3 and T3 sulfate by homogenates of cells transfected with rat ID-T cDNA and by rat liver microsomes. In both preparations rT3 is the pref erred substrate, while deiodination of T3 is markedly accelerated by i ts sulfation. Kinetic analysis provided similar K-m and V-max values i n cell homogenates and liver microsomes. These data demonstrate unequi vocally that ID-I is capable of both activating and inactivating thyro id hormone by ORD and IRD, respectively.