Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells.
T4, which is a major secretory product of the thyroid gland, needs to be converted to T3 by iodothyronine deiodinase to exert its biological activity. After the molecular cloning of human type II iodothyronine deiodinase (DII) complementary DNA, DII expression was unexpectedly detected in human skeletal muscle tissue. In the present study, we have identified DII activity and DII messenger ribonucleic acid (mRNA) in cultured human skeletal muscle cells and studied the mechanisms involved in the regulation of DII expression in those cells. All of the characteristics of the deiodinating activity in cultured human skeletal muscle cells were compatible with those of DII. Northern analysis has demonstrated that DII mRNA, approximately 7.5 kb in size, was expressed in cultured human skeletal muscle cells. DII mRNA and DII activity were rapidly increased by (Bu)2cAMP, forskolin, or beta-adrenergic agonists and were negatively regulated by thyroid hormones in cultured human skeletal muscle cells. Although interleukin-1beta and interleukin-6 did not decrease DII expression in cultured human skeletal muscle cells, tumor necrosis factor-alpha decreased DII expression in those cells in a dose-dependent manner. These data have demonstrated, for the first time, that DII activity and DII mRNA are present in cultured human skeletal muscle cells, and that the DII expression is stimulated by beta-adrenergic mechanisms through a cAMP-mediated pathway and is negatively regulated by thyroid hormones and tumor necrosis factor-alpha.
Hosoi
Y
Y
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Murakami
M
M
Mizuma
H
H
Ogiwara
T
T
Imamura
M
M
Mori
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000201:enzymology*; D009638:Norepinephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013963:Thyroid Hormones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014409:Tumor Necrosis Factor-alpha; D005576:Colforsin; D003994:Bucladesine; D007453:Iodide Peroxidase; D007545:Isoproterenol; D009638:Norepinephrine