Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 rats
Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 rats
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DOI：
10.1093/carcin/20.8.1567
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发表时间：
1999-08-01
期刊：
影响因子：
4.7
通讯作者：
Ito, A
中科院分区：
文献类型：
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作者：
Fujimoto, N;Onodera, H;Ito, A
为探讨曲酸(KA)致肿瘤的作用机制，对饲喂2%KA的F344大鼠甲状腺摄碘、血清促甲状腺激素(TSH)和甲状腺激素水平进行了剂量和时间依赖性研究。4周后，雄性大鼠甲状腺明显增生，摄取I-125仅为对照组的3%。血清三碘甲腺原氨酸(T-3)和甲状腺激素(T-4)水平分别从最初的0.61 ng/ml、4.0mU/dl降至0.36 ng/ml、1.7mU/dl，TSH水平上升7倍至15 ng/ml，女性对甲状腺重量和I-125摄取的影响不明显，但血清T-3、T-4和TSH水平变化与男性相似。血清T-3、T-4和TSH水平随时间的变化与甲状腺吸碘抑制有关，有机碘的形成仅在治疗3周后才观察到抑制。恢复正常饮食后，两种性别的血清T-3、T-4和TSH水平均在48小时内恢复正常。这些数据表明，KA主要通过抑制碘的摄入来干扰甲状腺功能，从而导致血清T-3和T-4的下降。脑下垂体促甲状腺激素的增加反过来会刺激甲状腺的增生，这种情况在KA停药后是可逆的。
To clarify the mechanism of tumorigenesis by kojic acid (KA), dose and time dependence of iodine uptake in the thyroid gland and serum thyroid stimulating hormone (TSH) and thyroid hormone levels were investigated in F344 rats fed a diet containing 2% KA, After 4 weeks, thyroid hyperplasia was apparent in males, associated with a decrease in I-125 Uptake into the thyroid gland to only 3% of that in controls. The serum triiodothyronine (T-3) and thyroxine (T-4) levels dropped to 0.36 ng/ml, 1.7 mu g/dl from the initial values of 0.61 ng/ml, 4.0 mu g/dl and TSH increased seven times to 15 ng/ml, In females, the effects on thyroid weight and I-125 uptake were less prominent, although the changes in serum T-3, T-4 and TSH levels were similar to those in males. Time-dependent changes in serum T-3, T-4 and TSH levels correlated with the inhibition of iodine uptake in the thyroid, Inhibition of organic iodine formation was only observed after 3 weeks treatment. On return to the control diet, normal serum T-3, T-4 and TSH levels became evident within 48 h in both sexes. These data suggest that KA interrupts thyroid function, primarily by inhibiting iodine intake, consequently causing a decrease in serum T-3 and T-4. Increased TSH from the pituitary gland in turn stimulates thyroid hyperplasia, which is reversible on withdrawal of KA.