Effect of dexamethasone on triiodothyronine production in the perfused rat liver and kidney.

Dexamethasone administration to rats decreases T4-5'-deiodinase activity in liver homogenates and slices and in isolated rat renal tubules. To determine if this decreased T4-5'-deiodinase activity results in decreased T3 production, rat livers and kidneys of control and dexamethasone-treated rats were perfused with medium containing free T4 concentrations approximating euthyroid rat serum, and net T3 production was measured by RIA. Dexamethasone administration decreased body weight by 14% but did not affect liver weight, kidney weight, or serum concentrations of T4 or T3. When livers were perfused with T4 concentrations of 10 micrograms/dl (free T4 = 6.5 ng/dl), hepatic T3 production, T4 uptake, and the conversion of T4 to T3 were similar in dexamethasone-treated rats and saline-treated controls. However, when livers were perfused at a T4 concentration of 125 micrograms/dl (free T4 = 81 ng/dl), dexamethasone-treated livers produced significantly less T3 than controls because of decreased conversion of T4 to T3. Hepatic deiodination of T3 and excretion of T3 into bile were not affected by dexamethasone. Renal T3 production, T4 uptake, and conversion of T4 to T3 was likewise unaffected by dexamethasone treatment when kidneys were perfused at near-normal free T4 concentrations. These studies indicate that dexamethasone treatment does not alter T3 production in the perfused liver and kidney and underscore the importance of using free T4 concentrations approximating physiologic levels when studying regulation of T3 production in individual organs.