Does glutathione regulate thyroxine deiodinase activity in cells?

Since iodothyronine monodeiodinase require reduced sulfhydryl groups to be active, and since hepatic nonprotein sulfhydryls are low in states associated with decreased formation of T3 from T4, a regulatory role for glutathione (GSH) has been postulated in thyroid hormone deiodination. Studies with cultured rat hepatocytes showed that a 90% decrease of total GSH, achieved by culturing cells in Cys, Met-deficient medium, did not alter 5'- or 5-deiodinase activity. The glutathione disulfide (GSSG) fraction remained constant, however. When the GSSG: total GSH ratio was increased by culturing the cells in 0.5 mM diamide, butylhydroperoxide, or 10(-5) M vinblastine, 5'-deiodination was decreased. In fetal mouse liver explants, 5'-deiodination and total GSH were decreased but the GSSG ratio was normal and the deiodinase Vmax was decreased. It is concluded that monodeiodinase activity in hepatocytes is not regulated by the total GSH concentration but is inversely correlated with the ratio of GSSG to total GSH.