Tsuchiya Y, Saji M, Isozaki O, Arai M, Tsushima T, Shizume K
Department of Medicine, Tokyo Women's Medical College, Japan.
Endocrinology. 1990 Jan;126(1):460-5. doi: 10.1210/endo-126-1-460.
We investigated the direct effect of lithium on porcine thyroid cells in culture to exclude the secondary regulatory factors. First we have studied the effect of lithium on TSH-induced iodide uptake. Significant suppression was seen at 0.1 mmol/liter, and half-maximal suppression was obtained at the pharmacological concentration reported in patient serum. The suppression was dose dependent and reversible. Besides the suppression of cAMP production stimulated by TSH, lithium also inhibited iodide uptake stimulated by forskolin or 8-bromo-cAMP. These results demonstrated that lithium inhibits TSH-induced iodide uptake not only by reducing cAMP production, but also by acting on the steps of post-cAMP production. Next, we studied the effect of lithium on DNA synthesis of the cultured porcine thyroid cells. Lithium stimulated [3H]thymidine incorporation of the thyroid cells in the basal condition (0.5% fetal calf serum) as well as those stimulated by insulin-like growth factor-I (100 micrograms/liter). The minimal concentrations for the significant increase were 0.5 and 0.1 mmol/liter, respectively. These results suggest that lithium might contribute to the formation of the goiter directly at the cellular levels in patients treated with the agent.
我们研究了锂对培养的猪甲状腺细胞的直接作用，以排除次级调节因子。首先，我们研究了锂对促甲状腺激素（TSH）诱导的碘摄取的影响。在0.1 mmol/升时可见显著抑制，在患者血清中报道的药理浓度下获得半数最大抑制。这种抑制呈剂量依赖性且可逆。除了抑制TSH刺激的环磷酸腺苷（cAMP）产生外，锂还抑制福司柯林或8-溴-cAMP刺激的碘摄取。这些结果表明，锂不仅通过减少cAMP产生来抑制TSH诱导的碘摄取，还通过作用于cAMP产生后的步骤来实现。接下来，我们研究了锂对培养的猪甲状腺细胞DNA合成的影响。锂在基础条件（0.5%胎牛血清）以及胰岛素样生长因子-I（100微克/升）刺激的情况下均刺激了甲状腺细胞的[3H]胸腺嘧啶核苷掺入。显著增加的最低浓度分别为0.5和0.1 mmol/升。这些结果表明，锂可能在接受该药物治疗的患者的细胞水平上直接促进甲状腺肿的形成。
