REGULATION OF TYPE-I 5'-DEIODINASE BY THYROID-HORMONE AND DEXAMETHASONE IN RAT-LIVER AND KIDNEY-CELLS

Type I 5'-deiodinase (5'D-I) is crucial for the generation of circulat ing 3,5,3'-triiodothyronine (T-3) and so is a major determinant of thy roid hormone action. Liver and kidney 5'D-I activity is reduced in non thyroidal illness (NTI), but the exact cause of reduced 5'D-I activity remains unknown. Elevated circulating glucocorticoid hormone concentr ations are one factor postulated to play a role. We have studied regul ation of 5'D-I expression in cultured rat liver (phi(1)) and kidney (N RK-52E) cells in response to treatment with T-3 and the glucocorticoid dexamethasone. 5'D-I mRNA was measured by Northern hybridization and 5'D-I activity was measured in a substrate conversion assay. Expressio n of the sodium pump alpha(1)-subunit (Na+/K+-ATPase alpha(1)-subunit) mRNA was measured as an index of T-3 and dexamethasone effects. In ph i(1) liver cells, T-3 increased 5'D-I mRNA by 76 +/- 17% and 5'D-I act ivity by 101 +/- 30% (all results mean +/- SEM; n = 9). Dexamethasone increased 5'D-I mRNA by 55 +/- 16% and 5'D-I activity by 128 +/- 6%. I n NRK-52E rat kidney cells, 5'D-I mRNA increased by 87 +/- 15% with T- 3 treatment and by 76 +/- 14% with dexamethasone. 5'D-I activity in NR K-52E cells was measurable only after stimulation by combined T-3 and dexamethasone treatment. Na+/K+-ATPase alpha 1-subunit mRNA expression was stimulated following T-3 and dexamethasone treatment in both cell lines. These results provide evidence for direct pretranslational reg ulation of 5'D-I by T-3 and dexamethasone in both rat liver and kidney cells. Our findings do not support the hypothesis that glucocorticoid s are directly responsible for inhibition of 5'D-I enzyme activity in NTI.