Dual Mechanisms of Regulation of Type I lodothyronine 5'-Deiodinase in the Rat Kidney, Liver, and Thyroid Gland Implications for the Treatment of Hyperthyroidism with Radiographic Contrast Agents
Abstract Introduction Alterations in thyroid hormone status and the administration of radiographic contrast agents can markedly influence iodothyronine metabolism and, in particular, the activity of type I 5'-deiodinase (51I). In the present studies, the mechanisms responsible for these effects have been reassessed. As previously reported, the addition of iopanoic acid (1OP) to broken cell preparations resulted in a competitive pattern of 5DI inhibition. However, the in vivo administration to rats of IOP or 3,3',5'-triiodothyronine (rT3) resulted in a noncompetitive pattern of inhibition of 51)I in the liver, kidney, and thyroid gland, whereby marked decreases in maximal enzyme velocity (Vx) were noted, with no change in the value of the Michaelis-Menten constant. In rats rendered hyperthyroid by the injection of 3,5,3'-triiodothyronine (T3), 5DI activity was significantly increased in the liver and the kidney. Alterations in thyroid hormone status also have important and direct "autoregulatory" effects on the cellular processes that metabolize these hormones (2). In the rat, hyperthyroidism results in a marked increase in the rate of "local" T3 production in the liver (3, 4). This effect is secondary, in part, to an increase in activity of type I 5'-deiodinase (51DI), the principal enzymatic process responsible for hepatic thyroxine (T4) to T3 conversion (5). In contrast to this activating effect of thyroid hormones on 5'DI in the liver (and kidney Radiographic contrast agents such as iopanoic acid (IOP) and sodium ipodate (NaIp) inhibit T4 to T3 conversion in man (7-9) and experimental animals (10-12), and offer an alternative to the thionamides in the treatment ofGraves' disease In tissue homogenates, IOP and NaIp act as competitive inhibitors of both 5D
