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 circulating 3,5,3'-triiodothyronine (T3) and so is a major determinant of thyroid hormone action. Liver and kidney 5'D-I activity is reduced in nonthyroidal illness (NTI), but the exact cause of reduced 5'D-I activity remains unknown. Elevated circulating glucocorticoid hormone concentrations are one factor postulated to play a role. We have studied regulation of 5'D-I expression in cultured rat liver (phi 1) and kidney (NRK-52E) cells in response to treatment with T3 and the glucocorticoid dexamethasone. 5'D-I mRNA was measured by Northern hybridization and 5'D-I activity was measured in a sub-strate conversion assay. Expression of the sodium pump alpha 1-subunit (Na+/K(+)-ATPase alpha 1-subunit) mRNA was measured as an index of T3 and dexamethasone effects. In ø1 liver cells, T3 increased 5'D-I mRNA by 76 +/- 17% and 5'D-I activity 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%. In NRK-52E rat kidney cells, 5'D-I mRNA increased by 87 +/- 15% with T3 treatment and by 76 +/- 14% with dexamethasone. 5'D-I activity in NRK-52E cells was measurable only after stimulation by combined T3 and dexamethasone treatment. Na+/K(+)-ATPase alpha 1-subunit mRNA expression was stimulated following T3 and dexamethasone treatment in both cell lines. These results provide evidence for direct pretranslational regulation of 5'D-I by T3 and dexamethasone in both rat liver and kidney cells. Our findings do not support the hypothesis that glucocorticoids are directly responsible for inhibition of 5'D-I enzyme activity in NTI.
Davies
P H
PH
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, UK.
Sheppard
M C
MC
Franklyn
J A
JA
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology*
D012333:RNA, Messenger; D014284:Triiodothyronine; D003907:Dexamethasone; D007453:Iodide Peroxidase; D000254:Sodium-Potassium-Exchanging ATPase