Antithyroid Properties of 3-Hydroxy-4(lH)-Pyridone: Antiperoxidase Activity and Effect on Thyroid Function*

Confirmation of the antithyroid properties of the recently identified goitrogen 3-hydroxy-4(lH)-pyridone (DHP) was obtained by studying its effects on thyroid hormone levels in mice fed a restricted iodine diet containing 1% (wt/wt) DHP. Besides producing hyperplastic goiters, the compound depressed serum T4 concentration, caused a marked elevation in serum T3 uptake and TSH, and caused a slight increase in T3 concentration relative to controls. The effects of DHP on thyroid function were consistent with the histological changes and similar to those reported with other active antithyroid compounds. However, DHP is chemically distinct from any hitherto recognized goitrogen. Its mode of action was further investigated by testing for antiperoxidase activity, because many known goitrogens are general peroxidase inhibitors. A pig thyroid peroxidase preparation and a commercial lactoperoxidase were used. Like the known antithyroid agents resorcinol and 6-methyl-2-thiouracil, DHP was a potent inhibitor of four t...