Triiodothyronine is required for the stimulation of type II 5′-deiodinase mRNA in rat brown adipocytes

Type II 5'-iodothyronine deiodinase (D2), produces triiodothyronine (T-3) and is stimulated by cold exposure via norepinephrine (NE) release in brown adipose tissue. Cultured rat brown adipocytes require T-3 for the adrenergic stimulation of D2 activity. D2 mRNA expression in cultured brown adipocytes is undetectable with the use of basal conditions or NE without T-3. Full D2 expression is achieved using NE + T-3, especially after prolonged T-3 exposure. beta(3)-Adrenergic agonists mimic the NE action, whereas cAMP analogs do not. Prolonged exposure to T-3 alone increases D2 mRNA. High T-3 doses (500 nM) inhibit the adrenergic stimulation of D2 activity while increasing D2 mRNA. The effects obtained with NE + T-3 or T-3 alone are suppressed by actinomycin, but not by cycloheximide, which leads to accumulation of short D2 mRNA transcripts. Prolonged or short exposure to T-3 did not change D2 mRNA half-life, but T-3 seemed to elongate it. In conclusion, T-3 is an absolute requirement for the adrenergic stimulation of D2 mRNA in brown adipocytes. T-3 upregulates D2 mRNA, an effect that might involve stimulation of factors required for transcription or for stabilization of D2 mRNA.