Inner ring monodeiodination of thyroxine and 3,5,3'-L-triiodothyronine in rat brain.

Abstract

To elucidate the metabolism of thyroid hormone in the central nervous system (CNS), 5-monodeiodinating activities were studied by incubating T4 or T3 with an aliquot of the P2 fraction of the rat brain in the presence of dithiothreitol and measuring the amounts of rT3 or 3,3'-L-diiodothyronine (3,3'-T2) produced by RIA. The production of rT3 or 3,3'-T2 was dependent upon duration of the incubation, amount of tissue used, temperature, and pH (the optimal pH was 8.0). These findings show that these reactions are enzymic in nature. For the conversion of T4 to rT3, the Km was estimated to be 1.33 microM, and the Vmax was 173 fmol/mg protein . min. For the conversion of T3 to 3,3'-T2, the Km was estimated to be 2.31 microM, and the Vmax was 94 fmol/mg protein . min. Both the conversion of T4 to rT3 and that of T3 to 3,3'-T2 were dependent on the concentration of dithiothreitol, but were not inhibited by propylthiouracil, the well known inhibitor of 5'-deiodinating activity. Both activities were mainly found in the synaptosomal fractions. The P2 fraction from fetal and neonatal rat brains had significantly higher activity than that from the adult brain. These findings demonstrate the presence of 5-monodeiodinating activities in the rat brain.