Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.

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Sugawara M, Sugawara Y, Wen K

Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.

Thyroid. 1999 May;9(5):513-8.

PubMed ID

10365684 [ View in PubMed

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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 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Methimazole	Thyroid peroxidase	Protein	Humans	Yes	Substrate Inhibitor	Details
Propylthiouracil	Thyroid peroxidase	Protein	Humans	Yes	Inhibitor	Details