Interference of polychlorinated biphenyls in hepatic and brain thyroid hormone metabolism in fetal and neonatal rats.
Interference of polychlorinated biphenyls in hepatic and brain thyroid hormone metabolism in fetal and neonatal rats.
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多氯联苯对胎儿和新生大鼠肝和脑甲状腺激素代谢的干扰。
DOI：
10.1006/taap.1993.1168
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发表时间：
1993
影响因子：
3.8
通讯作者：
A. Brouwer
中科院分区：
文献类型：
--
作者：
D. Morse;D. Groen;M. Veerman;C. J. V. Amerongen;H. Koeter;A. Prooije;T. Visser;J. Koeman;A. Brouwer
在妊娠第1天产前口服0.2、0.6和1.8毫克/千克体重的3，3 '，4，4'，5，5 '-六氯联苯（HCB）以及同时口服1毫克/千克3，3'，4，第2天至第18天，4 '-四氯联苯（TCB），含0.6 mg HCB/本研究观察了妊娠第1天体重（kg）对妊娠Wistar大鼠及其胎仔和子代甲状腺激素水平和外周甲状腺代谢的影响。在妊娠大鼠（妊娠第12天和第20天）和新生儿（产后第21天）中，血浆总甲状腺素和游离甲状腺素水平被六氯苯以剂量依赖的方式降低，而在妊娠第20天，只有六氯苯和三氯苯的联合剂量才能有效地将胎儿甲状腺激素水平降低65%。在胎儿和新生儿的全脑匀浆中检测了II型甲状腺素5 '-脱碘酶（5' D-II）的活性，该酶负责将甲状腺素（T4）脱碘为脑中具有生物活性的三碘甲状腺原氨酸。血浆甲状腺激素的减少伴随着胎儿（妊娠第20天）和新生儿（产后第7天和第21天）脑匀浆中5 'D-II活性的显著增加，高达100%。在0.6和1.8毫克六氯苯/千克剂量和合并剂量下，所有处理的胎儿（妊娠第20天）肝微粒体对125 I-T4的葡萄糖醛酸化至少比对照水平增加100%，新生儿（产后第7天和第21天）增加至少40%。这些数据表明，产前服用六氯苯和/或三氯苯会导致外周T4代谢增加。5 'D-II活性的增加表明，暴露于六氯苯和/或三氯苯的胎儿和新生大鼠的大脑中发生局部甲状腺功能减退。由于这些影响发生在甲状腺激素在大脑成熟中发挥重要作用的时期，它们可能有助于解释多氯联苯诱导的发育神经毒性机制。
The effects of prenatal oral administration of 0.2, 0.6, and 1.8 mg/kg body wt of 3,3',4,4'5,5'-hexachlorobiphenyl (HCB) on Day 1 of gestation and a combination of 1 mg/kg 3,3',4,4'-tetrachlorobiphenyl (TCB) from Day 2 to Day 18 with 0.6 mg HCB/kg body wt on Day 1 of gestation on thyroid hormone status and peripheral thyroid metabolism were studied in pregnant Wistar rats and their fetuses and offspring. Plasma total thyroxine and free thyroxine levels were reduced by HCB in a dose-dependent fashion in pregnant rats (Days 12 and 20 of gestation) and neonates (Day 21 postpartum), while only a combined dose of HCB and TCB was effective in decreasing fetal thyroid hormone levels by 65% on Day 20 of gestation. The activity of type II thyroxine 5'-deiodinase (5'D-II), the enzyme responsible for the deiodination of thyroxine (T4) to biologically active triiodothyronine in the brain, was examined in whole brain homogenates in fetuses and neonates. Decreases in plasma thyroid hormones were accompanied by significant increases, up to 100%, in 5'D-II activity in brain homogenates from fetuses (Day 20 of gestation) and neonates (Days 7 and 21 postpartum). The glucuronidation of 125I-T4 by hepatic microsomes was increased by at least 100% relative to control levels by all treatments in fetuses (Day 20 of gestation) and increased at least 40% in neonates (Days 7 and 21 postpartum) by a dose of 0.6 and 1.8 mg HCB/kg and the combined dose. These data indicate that prenatal HCB and/or TCB administration result in increased peripheral T4 metabolism. The increase in 5'D-II activity suggests that local hypothyroidism occurs in the brains of fetal and neonatal rats exposed to HCB and/or TCB. Since these effects occur during a period in which thyroid hormones play an important role in brain maturation, they may help explain the mechanism of developmental neurotoxicity induced by polychlorinated biphenyls.