Direct effect of methimazole on rat thyroidal cell growth induced by thyrotropin and insulin-like growth factor I

The direct effect of methimazole (MMI) on FRTL-5 cell growth was examined. TSH, (Bu)2cAMP, calf serum, insulin-like growth factor I, and Graves' immunoglobulin (IgG) increased [3H]thymidine incorporation into DNA during 72-h incubation. MMI (10(-3) M), which does not damage cell viability, significantly enhanced the increase in [3H]thymidine incorporation induced by TSH and (Bu)2cAMP. In contrast, MMI suppressed the increase in [3H]thymidine incorporation induced by calf serum, insulin-like growth factor I, and Graves' IgG. MMI had no effect on the production of cAMP by TSH. Accordingly, we concluded that MMI has opposite effects on cAMP- and non-cAMP-dependent cell growth pathways. Moreover, Graves' IgG, which has a modest effect on cAMP production, is believed to induce cell growth via the non-cAMP dependent cell growth pathway.