In FRTL-5 cells, methimazole (MMI) and propylthiouracil (PTU), both thyroid peroxidase (TPO) inhibitors, increase thyroglobulin (Tg) mRNA levels and Tg accumulation in the medium. An increase in Tg mRNA levels and in Tg accumulation was observed after 2-4 h and 8 h incubation with 10,000 microM MMI or PTU, respectively. Glutamate dehydrogenase mRNA levels, which corresponded with total RNA levels, were not affected. The concentrations of these drugs at which stimulation occurs are higher than the concentrations required for complete inhibition of TPO activity. The stimulatory effects of MMI and PTU can be suppressed by iodide and do not occur when protein synthesis is inhibited by cycloheximide. The effect of MMI on Tg gene expression is not dependent on thyrotropin (TSH) or insulin and MMI does not change the TSH-induced cAMP production. We conclude that MMI and PTU interfere in a regulatory pathway for Tg gene expression.
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