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Am J Physiol Endocrinol Metab 282: E1119-E1127, 2002; doi:10.1152/ajpendo.00433.2001
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Vol. 282, Issue 5, E1119-E1127, May 2002

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

Raquel Martinez-deMena, Arturo Hernández, and Maria-Jesús Obregón

Unidad de Endocrinología Molecular, Instituto de Investigaciones Biomédicas, Centro Mixto "Alberto Sols," Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28029 Madrid, Spain

Type II 5'-iodothyronine deiodinase (D2), produces triiodothyronine (T3) and is stimulated by cold exposure via norepinephrine (NE) release in brown adipose tissue. Cultured rat brown adipocytes require T3 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 T3. Full D2 expression is achieved using NE + T3, especially after prolonged T3 exposure. beta 3-Adrenergic agonists mimic the NE action, whereas cAMP analogs do not. Prolonged exposure to T3 alone increases D2 mRNA. High T3 doses (500 nM) inhibit the adrenergic stimulation of D2 activity while increasing D2 mRNA. The effects obtained with NE + T3 or T3 alone are suppressed by actinomycin, but not by cycloheximide, which leads to accumulation of short D2 mRNA transcripts. Prolonged or short exposure to T3 did not change D2 mRNA half-life, but T3 seemed to elongate it. In conclusion, T3 is an absolute requirement for the adrenergic stimulation of D2 mRNA in brown adipocytes. T3 upregulates D2 mRNA, an effect that might involve stimulation of factors required for transcription or for stabilization of D2 mRNA.

norepinephrine; uncoupling protein-1


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