Requirement of gene transcription and protein synthesis for cold- and norepinephrine-induced stimulation of thyroxine deiodinase in rat brown adipose tissue.
The increase in propylthiouracil-insensitive 'type II' thyroxine 5'-deiodinase activity of brown adipose tissue was investigated in rats exposed to acute cold stress or single-dose norepinephrine injection. The 20-fold cold-induced increase in enzyme activity showed a 2-h lag phase and reached a maximum after only 8 h; reacclimation occurred with a 2-h time lag and a half-life of 2.2 h. 4 h after a single norepinephrine injection, the deiodinase activity was almost identical to that after a 4-h cold stress; norepinephrine could not potentiate the effect of the cold stress. Treatment with the protein synthesis inhibitor cycloheximide before exposure to cold or before norepinephrine injection totally blocked the increase in deiodinase activity, suggesting that the increase is due to de novo protein synthesis. The half-life of the enzyme in vivo was estimated to be 0.7 h. Treatment with the RNA synthesis inhibitor actinomycin D totally abolished the cold- and norepinephrine-induced increases, indicating that the increase requires mRNA synthesis. It was concluded that the dramatic cold-induced increase in thyroxine deiodinase activity in brown adipose tissue was not due to activation of preexisting enzyme but was fully due to a norepinephrine-induced increase in expression of the gene and subsequent synthesis of the protein.
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D011441:Propylthiouracil / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013974:Thyroxine / Q000097:blood; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000097:blood
D012333:RNA, Messenger; D014284:Triiodothyronine; D011441:Propylthiouracil; D007453:Iodide Peroxidase; D013974:Thyroxine; D009638:Norepinephrine