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 µg/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 salinetreated controls. However, when livers were perfused at a T₄ concentration of 125 µg/dl (free T₄ = 81 ng/dl), dexamethasonetreated 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.