Korytkowski M, Cooper D
Division of Endocrinology and Metabolism, Sinai Hospital of Baltimore, MD.
Thyroid. 1992 Winter;2(4):345-50. doi: 10.1089/thy.1992.2.345.
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.
尽管已知抗甲状腺药物（ATD）通过抑制甲状腺滤泡细胞内的碘有机化发挥作用，但对其作用机制仍缺乏全面了解。本研究调查了甲巯咪唑（MMI）和丙硫氧嘧啶（PTU）对促甲状腺激素（TSH）和促甲状腺免疫球蛋白（TSI）刺激的FRTL-5细胞中环磷酸腺苷（cAMP）产生及生长的影响。MMI能抑制TSH刺激的cAMP产生，但PTU不能，且MMI仅在极高浓度（10⁻³ M）时才有此作用：分别为0.3±0.01与0.79±0.13 pmol/μg蛋白质（p<0.01）。在任何剂量下，MMI和PTU均不能抑制TSI刺激的cAMP产生。通过[³H] - 胸腺嘧啶核苷掺入法检测发现，MMI和PTU对TSH或TSI刺激的细胞生长均无抑制作用。这些观察结果表明，高浓度的MMI可能通过抑制受体介导的cAMP产生来控制甲状腺功能。尽管在ATD治疗期间甲状腺大小经常会减小，但MMI和PTU对TSH或TSI刺激的甲状腺细胞生长均无任何影响。
