Inhibition of thyroidal iodotyrosine deiodination by tyrosine analogues.

Abstract

The effect of several tyrosine derivatives on deiodination of 3,5-diiodo-L-tyrosine (DIT) has been examined in vitro and in vivo. In TPNH-supplemented sheep thyroid homogenates, the most effective inhibitors of deiodination, in order of increasing potency, were 3,5-dibromo-L-tyrosine (DBT), 3,5-dinitro- L-tyrosine (DNT) and 3-nitro-L-tyrosine (MNT); kinetic studies suggested purely competitive inhibition. Compounds with weak or no inhibitory activity included tyrosine itself, its 3-methyl-, 3-isopropyl-, 3-ra-propyl-, and 3- amino- derivatives, and 3,4-dihydroxy-L-phenylalanine. DBT, DNT and MNT also inhibited deiodination of DIT by sheep thyroid slices. In rats, administration of DBT, DNT, or MNT with 131I-DIT inhibited deiodination, and led to the appearance of an unknown DIT metabolite in blood and urine. Administration of the most potent in. vitro inhibitor, MNT, to rats prelabeled with radioiodine was followed by the urinary excretion of large amounts of a similar unknown organic iodine compound, together with small amounts of DIT and of monoiodotyrosine. This result suggests that MNT can inhibit the deiodination of endogenously formed iodotyrosines. (Endocrinology83: 336, 1968)