Correlation of hepatic thyroxine 5'-monodeiodination with hexose monophosphate shunt in young rats

The role of NADPH and glutathione (GSH) in hepatic thyroxine (T4) 5'-deiodination and possible metabolic linkage between T4 converting system ad hexose monophosphate shunt were studied in young rats during maturation. Low activity of T4 5'-deiodinase in young rats was enhanced 2-4-fold with the addition of 1 mM NADPH and GSH in vitro, the effect of which was more prominent with NADPH than with GSH. The highest enhancement was observed at 2-3 wk of age, whereas basal T4 5'-deiodinase activity was gradually increased until 5-6 wk of age, decreasing to adult level thereafter. This change was associated with a rise in GSH and glycogen content in the live and significantly correlated to the changes in glutathione reductase activity (r = 0.622, P less than 0.001). In contrast, glucose-6-phosphate dehydrogenase (G6PD) activity remained depressed until 5 wk of age and rose sharply thereafter. Between T4 5'-deiodinase and G6PD activities after 6 wk of age, an inverse correlation was noted (r = -0.749, P less than 0.01). A dose-response relationship between triiodothyronine (T3) production and NADPH in vitro showed similar age-related changes, whereas dose-dependency of T3-formation on GSH was decreasing with age, especially under the presence of 1 mM NADPH. These results indicate that: (1) NADPH and GSH are important cofactors of T4 conversion to T3; (2) NADPH appears to be more rate-limiting in the maturational process of the system; and (3) hexose monophosphate shunt plays a significant role in the regulation of T4 5'-monodeiodination through NADPH and GSH formation.