Type 2 iodothyronine deiodinase expression is upregulated by the protein kinase A-dependent pathway and is downregulated by the protein kinase C-dependent pathway in cultured human thyroid cells.
Type 1 and 2 iodothyronine deiodinases (D1 and D2) catalyze thyroxine (T4) activation. In human thyroid, unlike rodents', both D1 and D2 are expressed. We have investigated the effects of thyrotropin (TSH), dibutyryl cyclic adenosine monophosphate [(Bu)2cAMP] (an activator of protein kinase A [PKA]), 12-O-tetradecanoylphorbor 13-actate (TPA) (an activator of protein kinase C [PKC]), T4, and triiodothyronine (T3) on the D2 mRNA levels and activity in cultured human thyroid cells. D2 mRNA levels were increased by TSH and (Bu)2cAMP, and the increment was faster and greater than that of D1 mRNA levels. The increment of the maximum velocity (Vmax) value for D2 by (Bu)2cAMP stimulation was similar to that of D2 mRNA levels, suggesting that (Bu)2cAMP enhances D2 activity mainly at the pretranslational level. Cycloheximide, a protein synthesis inhibitor, partially inhibited the increase of D2 mRNA levels by (BU)2cAMP, suggesting that de novo protein synthesis-dependent pathways are involved. TPA suppressed the D2 mRNA levels in the presence of (Bu)2cAMP. However, T3 and T4 did not significantly change the D2 mRNA levels and activity. In conclusion, D2 expression in human thyroid cells is more rapidly and strongly upregulated by the PKA pathway than D1 expression, and is downregulated by the PKC pathway.
Imai
Y
Y
Second Department of Internal Medicine, Kansai Medical University, Moriguchi-City, Osaka, Japan.
Toyoda
N
N
Maeda
A
A
Kadobayashi
T
T
Fangzheng
G
G
Nishikawa
M
M
Iwasaka
T
T
D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D011493:Protein Kinase C / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D000097564:Iodothyronine Deiodinase Type II
D003994:Bucladesine; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D003513:Cycloheximide; D007453:Iodide Peroxidase; D011493:Protein Kinase C; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate; D013972:Thyrotropin; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II