Antithyroid drug effects on function and growth of FRTL-5 cells

Although antithyroid drugs (ATDs) are known to exert their effects by inhibiting iodide organification within the thyroid follicular cell, a full understanding of their mechanisms of action is lacking. In this study the effects of methimazole (MMI) and propylthiouracil (PTU) on thyrotropin (TSH) and thyroid-stimulating immunoglobin (TSI)-stimulated cAMP production and growth in FRTL-5 cells was investigated. MMI, but not PTU, inhibited TSH-stimulated cAMP production, but only at the very highest concentration (10(-3) M): 0.3 +/- 0.01 vs 0.79 +/- 0.13 pmol/micrograms protein (p < 0.01). Neither MMI nor PTU inhibited TSI-stimulated cAMP production at any dose. Neither MMI nor PTU exhibited an inhibitory effect on TSH- or TSI-stimulated cell growth, as measured by [3H]-thymidine incorporation. These observations suggest that high concentrations of MMI may act to control thyroid function by inhibiting receptor-mediated cAMP production. Although decreases in thyroid gland size frequently occur during ATD therapy, neither MMI nor PTU exhibited any effect on TSH- or TSI-stimulated thyroid cell growth.