Methimazole and Propylthiouracil Increase Cellular Thyroid Peroxidase Activity and Thyroid Peroxidase mRNA in Cultured Porcine Thyroid Follicles

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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 μM KI for 2 days. TPO activity was measured in the 100,000 × g-pellet of the thyroid sonicate by the guaiacol oxidation method. Exposure to MMI (1 μM and 10 μ,M) or PTU (10 μM and 100 μM) for 2 days caused a significant increase in cellular TPO activity; 100 μM 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.