High affinity of triiodothyronine (T3) for nonphenolic ring deiodinase and high affinity of tetraiodothyroacetic acid (TETRAC) for phenolic ring deiodinase in cultured monkey hepatocarcinoma cells and in rat liver homogenates

Abstract

The metabolism of 3, 5-[3'-125I]triiodothyronin (T3) and 3-[3', 5'-125I]triiodothyronine (rT3) was studied in cultured monkey hepatocarcinoma cells (NCLP-6E), and the deiodinations of these iodothyronines were also investigated in cultured cell homogenates and in rat liver homogenates. The metabolites were analyzed by ion exchange column chromatography. For nonphenolic ring deiodination of 3, 5-[3'-125I]triiodothyronine, the order of the inhibitory effect of excess unlabeled iodothyronine or its analog was as follows: 3,3',5-triiodothyroinine greater than triiodothyroacetic acid greater than tetraiodothyroacetic acid greater than thyroxine. This order did not differ between in the intact cells (NCLP-6E) and their homogenates. The order of effectiveness of the excess unlabeled compounds on phenolic ring deiodination of 3-[3', 5'-125I]triiodothyronine in the intact cells was as follows: tetraiodothyroacetic acid greater than triiodothyroacetic acid, 3, 3', 5-triiodothyronine greater than thyroxine. This order was the same among monkey hepatocarcinoma cell homogenates, rat hepatoma cell homogenates and rat liver homogenates, and triiodothyroacetic acid was obviously more effective than 3, 3', 5-triiodothyronine. It was concluded that 3, 3', 5-triiodothyronine had the highest affinity for nonphenolic ring deiodinase among iodothyronines and their analogs used in the present study and that tetraiodothyroacetic acid and the highest affinity for phenolic ring deiodinase. It seems, therefore, that the metabolites derived from the thyroid hormones might contribute to deiodinations which involve activation and inactivation of the hormones.