Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.
Methimazole (MMI) and propylthiouracil (PTU) are common antithyroid drugs for treating hyperthyroidism because the 2 drugs inhibit thyroid peroxidase (TPO)-catalyzed thyroid hormone formation. We studied whether the 2 drugs actually inhibit cellular TPO activity in cultured porcine follicles. Porcine follicles were cultured in the presence of 1 mU/mL thyrotropin (TSH) for 7 days. Then follicles were exposed to MMI or PTU in the presence of 0.1 microM Kl for 2 days. TPO activity was measured in the 100,000 x g-pellet of the thyroid sonicate by the guaiacol oxidation method. Exposure to MMI (1 microM and 10 microM) or PTU (10 microM and 100 microM) for 2 days caused a significant increase in cellular TPO activity; 100 microM MMI inhibited cellular TPO activity. The presence of cyclic adenosine monophosphate (cAMP)-generating system (forskolin) in TSH-free medium increased MMI-mediated TPO activity. Cyclohexamide inhibited MMI-mediated TPO activation, indicating that new protein synthesis is required for increased TPO activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in TPO mRNA by PTU or MMI. In conclusion, MMI and PTU at therapeutic concentrations can increase TPO mRNA and cellular TPO activity, although the 2 drugs inhibit the TPO-H2O2-mediated catalytic reaction.
Sugawara
M
M
West Los Angeles Veterans Affair Medial Center and Department of Medicine, UCLA School of Medicine, California 90073, USA. msugawar@ucla.edu
Sugawara
Y
Y
Wen
K
K
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism*; D008713:Methimazole / Q000494:pharmacology*; D011193:Potassium Iodide / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D011193:Potassium Iodide; D005576:Colforsin; D008713:Methimazole; D011441:Propylthiouracil; D003513:Cycloheximide; D007453:Iodide Peroxidase