Acute posttranscriptional regulation of cerebrocortical and pituitary iodothyronine 5'-deiodinases by thyroid hormone.
Cerebrocortical and pituitary iodothyronine 5'-deiodinases produce 50% or more of the T3 found in these tissues and show rapid 3- to 5-fold changes in response to changes in the thyroid status. Since many T3 responses are initiated in the cell nucleus and require protein synthesis, we studied the influence of cycloheximide and actinomycin D on the acute T3 suppression of cerebrocortical and pituitary 5'-deiodinase activities in hypothyroid rats. Cycloheximide inhibited protein synthesis by more than 95%, but did not prevent the rapid (4-h) T3-mediated decreases in 5'-deiodinase activity. In the presence of cycloheximide, T3 decreased enzyme activity by more than 85%, with a t1/2 of approximately 70 min in the cerebral cortex and about 110 min in the pituitary. In vitro, neither T3 nor cycloheximide in large excess had any effect on enzyme activity. In cycloheximide-treated rats, cerebrocortical 5'-deiodinase activity decreased with a fractional turnover rate (k) of 1.2 h-1 in euthyroid and 0.07 h-1 in hypothyroid rats, respectively, with corresponding steady state enzyme levels of 18 +/- 3 and 145 +/- 9 U/mg protein. The resulting production rates of cerebrocortical 5'-deiodinase were 22 and 10 U/mg protein X h. Actinomycin D failed to alter either the cerebrocortical 5'-deiodinase in euthyroid rats in 4 h or the inhibitory effect of T3, but inhibited RNA synthesis by more than 70%. These data indicate that the T3-dependent fall in cerebrocortical 5'-deiodinase is mediated by a posttranscriptional mechanism that ultimately increases the rate of degradation/inactivation of the enzyme.
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003513:Cycloheximide / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology*; D004347:Drug Interactions; D007453:Iodide Peroxidase / Q000235:genetics*; D007700:Kinetics; D008297:Male; D010544:Peroxidases / Q000235:genetics*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D003609:Dactinomycin; D003513:Cycloheximide; D010544:Peroxidases; D007453:Iodide Peroxidase