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Sugawara
Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.Sugawara M, Sugawara Y, Wen K. Thyroid. 1999 May;9(5):513-8. [no 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." |
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