title: Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.
abstract: 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.
authors.affiliation: West Los Angeles Veterans Affair Medial Center and Department of Medicine, UCLA School of Medicine, California 90073, USA. msugawar@ucla.edu
authors.forename: M
authors.initials: M
authors.lastname: Sugawara
authors.forename: Y
authors.initials: Y
authors.lastname: Sugawara
authors.forename: K
authors.initials: K
authors.lastname: Wen
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D011193:Potassium Iodide; D005576:Colforsin; D008713:Methimazole; D011441:Propylthiouracil; D003513:Cycloheximide; D007453:Iodide Peroxidase