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.

Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells

“…Our finding that PTU in the absence of iodide increased NIS and hCG mRNA and iodide uptake is interesting. PTU has previously been reported to have effects on gene expression including reduction of NIS mRNA and iodide uptake in FRTL-5 cells (30), increased TPO mRNA in cultured porcine follicles (31), and thyroglobulin mRNA expression (32) in FRTL-5 cells. We acknowledge, however, that the mechanism of this effect of PTU on gene regulation is uncertain.…”

Retinoic acid induces sodium/iodide symporter gene expression and radioiodide uptake in the MCF-7 breast cancer cell line

“…The value was normalized to the cellular protein content measured in the same cells with Bio-Rad protein assay. The activity of peroxidase was measured as described (35).…”

Comparative Study on the Binding Affinity of Methimazole and Propylthiouracil to Thyroid Peroxidase as an Anti-Thyroid Drug: An Insilico Approach

“…The drug binding mechanism of PTU/MMZ to TPO have only been done in-vivo [36][37][38][39], however the molecular insights are yet to be understood. Due to the close homology, LPO has been used as surrogates to study interaction of TPO with anti-Thyroid drug MMZ.…”