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.
Division of Endocrinology and Metabolism, Sinai Hospital of Baltimore, MD.
M
M
Korytkowski
D
D
Cooper
D000818:Animals; D000906:Antibodies; D001323:Autoantibodies / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D018828:Immunoglobulins, Thyroid-Stimulating; D008713:Methimazole / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013972:Thyrotropin / Q000494:pharmacology
D000906:Antibodies; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D008713:Methimazole; D011441:Propylthiouracil; D013972:Thyrotropin; D004247:DNA; D000242:Cyclic AMP