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.
Martinez-deMena
Raquel
R
Unidad de Endocrinología Molecular, Instituto de Investigaciones Biomédicas, Centro Mixto "Alberto Sols," Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Hernández
Arturo
A
Obregón
Maria-Jesús
MJ
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007453:Iodide Peroxidase / Q000235:genetics*; D007473:Ion Channels; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D009638:Norepinephrine / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology*; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II
D000316:Adrenergic alpha-Agonists; D002352:Carrier Proteins; D003609:Dactinomycin; D004983:Ethanolamines; D007453:Iodide Peroxidase; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009638:Norepinephrine; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D014284:Triiodothyronine; D000071256:Uncoupling Protein 1; D000097564:Iodothyronine Deiodinase Type II; C057368:BRL 37344