2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) EFFECTS ON HEPATIC-MICROSOMAL STEROID-METABOLISM AND SERUM ESTRADIOL OF PREGNANT RATS
2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) EFFECTS ON HEPATIC-MICROSOMAL STEROID-METABOLISM AND SERUM ESTRADIOL OF PREGNANT RATS
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DOI：
10.1016/0006-2952(83)90616-0
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发表时间：
1983-01-01
影响因子：
5.8
通讯作者：
MUTHER, TF
中科院分区：
文献类型：
--
作者：
SHIVERICK, KT;MUTHER, TF
进行实验以评估妊娠期间施用低剂量但具有胎儿毒性的 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 对肝微粒体中类固醇代谢的影响。口服1.mu.g.cntdot。 kg-1 .cntdot。妊娠第 7-19 天的妊娠大鼠第 1 天服用 TCDD 可减少妊娠期间母亲的体重增加。第 20 天的窝分析显示，经 TCDD 处理的母猪的胎儿出现以肠道出血为特征的内脏病变的发生率为 66%。在妊娠第 20 天，从经 TCDD 处理的母鼠制备的肝微粒体中细胞色素 P-450 含量增加了 2-3 倍，同时连二亚硫酸盐还原 CO 光谱的吸光度最佳值移至 448 nm。 TCDD 处理的母鼠肝微粒体中儿茶酚雌激素形成活性降低了 50-75%。暴露于 TCDD 后，微粒体中睾酮的 7.α-羟基化增加了近 4 倍，而 16.α-和 6.β-羟化酶活性没有变化。与 TCDD 治疗相关的儿茶酚雌激素形成的抑制并不反映微粒体类固醇羟化酶活性的普遍降低。由于儿茶酚雌激素形成在生理上是雌激素代谢的主要途径，因此在妊娠第4-15天用TCDD治疗的第二组妊娠大鼠中测量17β-雌二醇的血清浓度。在妊娠的这个阶段，对照母鼠和治疗母鼠的血清雌二醇水平没有差异。该研究显然不支持在体外肝微粒体中测量的 TCDD 介导的儿茶酚雌激素形成抑制与妊娠期间体内循环雌二醇水平改变之间的联系。
Experiments were conducted to evaluate the effects of administration of low, but fetotoxic quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during pregnancy on steroid metabolism in liver microsomes. Oral administration of 1 .mu.g .cntdot. kg-1 .cntdot. day-1 of TCDD to pregnant rats on days 7-19 of gestation reduced maternal weight gain during pregnancy. Analysis of litters on day 20 showed that fetuses from TCDD-treated dams had a 66% incidence of visceral lesions characterized by intestinal hemorrhage. Liver microsomes prepared from TCDD-treated dams on day 20 of gestation exhibited a 2-3-fold increase in cytochrome P-450 content which was accompanied by a shift in the absorbance optimum of the dithionite reduced-CO spectrum to 448 nm. Catechol estrogen formation activity was decreased by 50-75% in hepatic microsomes from TCDD-treated dams. 7.alpha.-Hydroxylation of testosterone increased nearly 4-fold, while 16.alpha.- and 6.beta.-hydroxylase activities were unchanged in microsomes following exposure to TCDD. The inhibition of catechol estrogen formation associated with TCDD treatment did not reflect a general decrease in microsomal steroid hydroxylase activities. Insofar as catechol estrogen formation is physiologically a major pathway for estrogen metabolism, serum concentrations of 17.beta.-estradiol were measured in a second group of pregnant rats treated with TCDD on days 4-15 of gestation. Serum estradiol levels were not different between control and treated dams at this stage of pregnancy. The study evidently does not support a link between TCDD-mediated inhibition of catechol estrogen formation measured in vitro in liver microsomes and altered circulating estradiol levels in vivo during pregnancy.