Effects of microsomal enzyme inducers on outer-ring deiodinase activity toward thyroid hormones in various rat tissues
Effects of microsomal enzyme inducers on outer-ring deiodinase activity toward thyroid hormones in various rat tissues
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DOI：
10.1006/taap.1999.8883
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发表时间：
2000-03-15
影响因子：
3.8
通讯作者：
Klaassen, CD
中科院分区：
文献类型：
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作者：
Hood, A;Klaassen, CD
微粒体酶诱导剂，如苯巴比妥 (PB)、孕烯醇酮 16 α-甲腈 (PCN)、3-甲基胆蒽 (3MC) 和 Aroclor 1254 (PCB) 在降低血清甲状腺素 (T-4) 方面比血清三碘甲状腺原氨酸 (T-3) 更有效。用 PB 和 PCN 治疗的大鼠可能通过增加血清 TSH（刺激甲状腺合成更多 T-3）来维持血清 T-3。然而，尚不清楚用 3MC 或 PCB 治疗的大鼠中血清 T-3 是如何维持的，因为这些大鼠中血清 TSH 并未增加。我们推测，在 I 型和 II 型外环脱碘酶 (ORD) 的催化下，T-4 向 T-3 的转化增加是用 3MC 或 PCB 治疗的大鼠中血清 T-3 得以维持的原因。此外，3MC和PCB不会增加血清TSH，而PB和PCN却会增加，因为3MC和PCB处理的大鼠垂体中的II型ORD活性比用PB或PCN处理的大鼠增加得更多。为了测试这两个假设，给雄性 Sprague-Dawley 大鼠喂食基础饮食或含有 PB（300、600、1200 或 2400 ppm）、PCN（200、400、800 或 1600 ppm）、3MC（50、100、200 或 400 ppm）或 PCB（25、 50、100 或 200 ppm），持续 7 天。 I 型 ORD 活性在甲状腺、肾脏和肝脏中测量，而 II 型 ORD 活性在棕色脂肪组织、垂体和大脑中测量。甲状腺中的 I 型 ORD 活性不受 PB、3MC 或 PCB 治疗的影响，并且 PCN 略有增加。肾脏中的 I 型 ORD 活性不受 PB、PCN 或 3MC 治疗的影响，并因 PCB 治疗而降低。 PB、PCN、3MC 和 PCB 治疗可降低肝脏中 I 型 ORD 活性。棕色脂肪组织中的 II 型 ORD 活性不受四种处理中任何一种的影响。垂体中的 II 型 ORD 活性不受 PB 或 3MC 处理的影响，并且通过 PCN 或 PCB 处理而增加。大脑中的 II 型 ORD 活性不受 PB 处理的影响，并且通过 PCN、3MC 和 PCB 处理而增加。总体而言，通过甲状腺、肾脏、肝脏、棕色脂肪组织、垂体和大脑中 ORD 活性的总和计算得出的总 ORD 活性被四种微粒体酶诱导剂减少而不是增加。总之，T-4 向 T-3 转化的增加并不是 3MC 或 PCB 治疗大鼠血清 T-3 浓度得以维持的原因。此外，3MC 和 PCB 处理的大鼠血清 TSH 不增加的原因是垂体中 II 型 ORD 活性增加以外的机制的结果。 (C) 2000 年学术出版社。
Microsomal enzyme inducers, such as phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), 3-methylcholanthrene (3MC), and Aroclor 1254 (PCB) are more effective at reducing serum thyroxine (T-4) than serum triiodothyronine (T-3). It is possible that rats treated with PB and PCN maintain serum T-3 by increasing serum TSH, which stimulates the thyroid gland to synthesize more T-3. However, it is unclear how serum T-3 is maintained in rats treated with 3MC or PCB, because serum TSH is not increased in these rats. We hypothesized that increased conversion of T-4 to T-3, catalyzed by outer-ring deiodinases (ORD) type-I and -II, is the reason serum T-3 is maintained in rats treated with 3MC or PCB. Furthermore, 3MC and PCB do not increase serum TSH, whereas PB and PCN do, because type-II ORD activity in the pituitary of 3MC- and PCB-treated rats is increased greater than in rats treated with PB or PCN. To test these two hypotheses, male Sprague-Dawley rats were fed either a basal diet or a diet containing PB (300, 600, 1200, or 2400 ppm), PCN (200, 400, 800, or 1600 ppm), 3MC (50, 100, 200, or 400 ppm), or PCB (25, 50, 100, or 200 ppm) for 7 days. Type-I ORD activity was measured in thyroid, kidney, and liver, whereas type-II ORD activity was measured in brown adipose tissue, pituitary, and brain. Type-I ORD activity in thyroid was not affected by PB, 3MC, or PCB treatments, and was slightly increased by PCN. Type-I ORD activity in kidney was not affected by PB, PCN, or 3MC treatments, and was reduced by PCB treatment. Type-I ORD activity in liver was reduced by PB, PCN, 3MC, and PCB treatments. Type-II ORD activity in brown adipose tissue was unaffected by any of the four treatments. Type-II ORD activity in pituitary was unaffected by PB or 3MC treatments, and was increased by PCN or PCB treatments. Type-II ORD activity in brain was unaffected by PB treatment, and was increased by PCN, 3MC, and PCB treatments. Overall, total ORD activity, calculated by summation of ORD activities in thyroid, kidney, liver, brown adipose tissue, pituitary, and brain, was reduced rather than increased by the four microsomal enzyme inducers. In conclusion, increased conversion of T-4 to T-3 is not the reason serum T-3 concentration is maintained in 3MC- or PCB-treated rats. Furthermore, the reason serum TSH is not increased in 3MC- and PCB-treated rats is the result of mechanisms other than increased type-II ORD activity in pituitary. (C) 2000 Academic Press.