EFFECTS OF ORAL ERYTHROSINE (2',4',5',7'-TETRAIODOFLUORESCEIN) ON THE PITUITARY THYROID AXIS IN RATS
EFFECTS OF ORAL ERYTHROSINE (2',4',5',7'-TETRAIODOFLUORESCEIN) ON THE PITUITARY THYROID AXIS IN RATS
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DOI：
10.1016/0041-008x(90)90327-q
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发表时间：
1990-05-01
影响因子：
3.8
通讯作者：
WITORSCH, RJ
中科院分区：
文献类型：
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作者：
JENNINGS, AS;SCHWARTZ, SL;WITORSCH, RJ
赤藓红（FD&C Red Dye No.3）是荧光素的四碘化衍生物。大鼠在子宫内开始喂食4%赤藓红饮食30个月，甲状腺腺瘤和腺癌的发病率增加。这些肿瘤可能是继发于TSH对甲状腺的刺激增加。本研究旨在确定饮食赤藓红是否会破坏垂体-甲状腺轴，从而改变血清甲状腺激素水平。TSH水平，或垂体对TRH的反应。给大鼠喂食含赤藓红（0.5、1.0、4.0%）、碘化钠（0.16%）或荧光素（1.6%）的饲料3周，之后进行体内TRH测试。赤藓红使血清T4水平呈剂量依赖性增加。与4%赤藓红饮食，血清T4和T3水平和游离T4指数显着增加，而游离T3指数不变。喂食4.0%赤藓红饮食的大鼠对TRH有夸大的TSH反应; TRH注射后10分钟，血清TSH水平比对照大鼠的TSH水平高80%。对大鼠短期给予赤藓红通过降低T4向T3的转化而降低了肝脏T2的产生，表明赤藓红降低了肝脏5“-脱碘酶活性。这些数据表明，饮食摄入4%赤藓红破坏垂体-甲状腺轴，如TSH对TRH的反应增加所证明的。这种效应是由赤藓红或碘化代谢物介导的，因为摄入其荧光素核没有影响。由于血清T4和T3水平升高，而碘给药并不增加促甲状腺激素对TRH的反应，因此，红细胞素的作用不太可能由碘介导。这些数据表明，赤藓红通过改变促甲状腺细胞T4向T3的转化来增加垂体对TRH的TSH反应。长期摄入赤藓红可通过TSH对甲状腺的长期刺激促进大鼠甲状腺肿瘤的形成。
Erythrosine (FD&C Red Dye No.3) is a tetraiodinated derivative of fluorescein. Rats fed a 4% erythrosine diet for 30 months beginning in utero have an increased incidence of thyroid adenomas and adenocarcinomas. These tumors may be secondary to increased stimulation of the thyroid glands by TSH. This study was undertaken to determine if dietary erythrosine disrupts the pituitary-thyroid axis thereby altering serum thyroid hormone levels. TSH levels, or the pituitary''s response to TRH. Rats were fed diets containing erythrosine (0.5, 1.0, 4.0%), sodium iodide (0.16%), or fluorescein (1.6%) for 3 weeks, after which TRH testing was performed in vivo. Erythrosine produced a dose-dependent increase in serum T4 levels. With the 4% erythrosine diet, serum T4 and T3 levels and the free-T4 index were significantly increased, whereas the free-T3 index was unchanged. Rats fed the 4.0% erythrosine diet had an exaggerated TSH response to TRH; 10 min after the TRH injection, serum TSH levels were 80% greater than TSH levels of control rats. Short-term administration of erythrosine to rats decreased hepatic T2 production by decreasing its conversion of T4 to T3, indicating that erythrosine decreases hepatic 5''-deiodinase activity. These data demonstrated the dietary ingestion of 4% erythrosine disrupts the pituitary-thyroid axis as evidenced by an increased TSH response to TRH. This effect is mediated by erythrosine or an iodinated metabolite, since ingestion of its fluorescein nucleus had no effect. Erythrosine''s effects were not likely mediated by iodide, because serum T4 and T3 levels were elevated and iodide administration did not increase the TSH response to TRH. These data suggest that erythrosine increases the pituitary''s TSH response to TRH by altering thyrotroph cell conversion of T4 to T3. Chronic erythrosine ingestion may promote thyroid tumor formation in rats via chronic stimulation of the thyroid by TSH.