DOSE-RESPONSE AND TIME COURSE OF HYPOTHYROXINEMIA AND HYPOINSULINEMIA AND CHARACTERIZATION OF INSULIN HYPERSENSITIVITY IN 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) TREATED RATS
DOSE-RESPONSE AND TIME COURSE OF HYPOTHYROXINEMIA AND HYPOINSULINEMIA AND CHARACTERIZATION OF INSULIN HYPERSENSITIVITY IN 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) TREATED RATS
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DOI：
10.1016/0300-483x(87)90031-x
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发表时间：
1987-06-01
期刊：
影响因子：
4.5
通讯作者：
ROZMAN, K
中科院分区：
文献类型：
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作者：
GORSKI, JR;ROZMAN, K
雄性Sprague-Dawley大鼠腹腔注射不同剂量的2，3，7，8-四氯二苯并对二恶英（TCDD）玉米油溶液。在几个时间点的促甲状腺激素（TSH），总甲状腺素（TT 4），游离甲状腺素（FT 4），总三碘甲状腺原氨酸（TT 3），反三碘甲状腺原氨酸（rT 3）和胰岛素测定血清中使用放射免疫法，葡萄糖氧化酶法测定葡萄糖。TSH和TT 3在任何测量时间点均不受任何剂量的影响。给药后第2 - 4天，TT 4和FT 4以某种剂量依赖性方式降低。TCDD给药后第32天，TT 4和FT 4恢复到正常值也呈剂量依赖性，但大鼠死亡较晚。rT 3也在每个剂量水平早期降低，并以某种剂量依赖性方式恢复至正常水平。给药后第8天，2个最高剂量组的大鼠出现低胰岛素血症，最高剂量组也出现低血糖。血清胰岛素和葡萄糖在TCDD的非幸存者中一直受到抑制，直到死亡。在存活者中，血清胰岛素在给药后第32天恢复至正常值。低胰岛素血症状态的特征还在于对胰岛素的超敏反应，即在施用125 μ g/kg TCDD后3天注射其它无毒剂量的胰岛素在24小时内对80%的大鼠是致死的。胰岛素超敏反应先于低血糖和低胰岛素血症。这些研究结果表明，低甲状腺素血症和hypoinsulinemia可能是一个适应性过程的一部分，大鼠试图减少毒性损伤的TCDD。
Male Sprague-Dawley rats were administered i.p. various doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in corn oil. At several time points thyroid stimulating hormone (TSH), total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), reverse triiodothyronine (rT3) and insulin were determined in serum using radioimmunoassays, and glucose was measured by the glucose oxidase method. TSH and TT3 were not affected by any dose at any time point of measurement. TT4 and FT4 were decreased in a somewhat dose-dependent manner by days 2 to 4 after dosing. Return of TT4 and FT4 to normal values by day 32 after TCDD dosage also occurred in a dose-dependent manner, except in rats that died later. rT3 was also decreased at each dose level early and returned to normal levels in a somewhat dose-dependent fashion. Rats in the 2 highest dose groups became hypoinsulinemic and in the highest dose group also hypoglycemic by day 8 after dosing. Serum insulin and glucose remained suppressed in non-survivors of TCDD until death ensued. In survivors, serum insulin returned to normal values by day 32 after dosing. The hypoinsulinemic state was further characterized by hypersensitivity towards insulin, i.e. injection of an otherwise non-toxic dose of insulin 3 days after administration of 125 .mu.g/kg TCDD was lethal to 80% of the rats within 24 h. Insulin hypersensitivity preceded both hypoglycemia and hypoinsulinemia. These findings suggest that hypothyroxinemia and hypoinsulinemia may be part of an adaptive process whereby rats attempt to diminish the toxic insult of TCDD.