Triclosan is a potent inhibitor of estradiol and estrone sulfonation in sheep placenta.
Triclosan is a potent inhibitor of estradiol and estrone sulfonation in sheep placenta.
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DOI：
10.1016/j.envint.2009.02.004
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发表时间：
2010-11
影响因子：
11.8
通讯作者：
Wood CE
中科院分区：
文献类型：
--
作者：
James MO;Li W;Summerlot DP;Rowland-Faux L;Wood CE
个人护理产品三氯生，5-氯-2(2，4-二氯苯氧基)-苯酚，在消费品中被广泛用作抗菌剂，并作为污水污泥和废水的污染物越来越多地存在于环境中。在美国、瑞典和澳大利亚人的血浆和尿液中已经发现了这种化合物。已知三氯生可抑制酚类异物的磺化反应，在结构上与雌激素磺基转移酶抑制剂有关，如多氯联苯。在妊娠期间，胎盘是雌激素的重要来源，而雌激素是胎儿正常发育和顺利分娩所必需的，而雌激素磺基转移酶被认为在调节雌激素供应方面发挥着重要作用。本研究以17-β-雌二醇和雌酮为底物，研究了三氯生对绵羊胎盘胞浆磺基转移酶活性的影响。作为比较，我们研究了4-羟基-3，3‘，4’，5-四氯联苯和2‘-羟基三氯卡班对雌二醇磺化反应的影响。以雌二醇为底物的胎盘胞浆磺基转移酶活性的表观Km为0.27±0.06 nM(3例)，以雌酮为底物的表观Km为1.86±0.22 nM。雌激素浓度高于10-20 nM时，观察到部分底物抑制，这是其他物种中典型的雌激素磺基转移酶(SULT1E1)。用不同浓度的雌二醇(0.1-6 nM)和雌酮(2 NM)研究了三氯生对雌激素转硫酶活性的影响。三氯生对雌二醇和雌酮磺化反应都有很强的抑制作用。雌二醇的抑制作用为竞争性/非竞争性混合抑制，KIC为0.09±0.01 nM，KiU为5.2±2.9 nM。抑制雌酮磺化的IC50为0.60±0.06 nM。在与环境有关的1μM浓度下，三氯生不是绵羊胎盘微粒体中葡萄糖醛酸化的底物。三氯生在胎盘胞浆中可被磺化，其Km值为1.14±0.18pm ol/μ/mg蛋白，Vmax为160±26pmoL/m in/mg蛋白，但在抑制雌激素磺化的低NM浓度下，计算的三氯生磺化速率可忽略不计。三氯生作为雌激素磺基转移酶活性抑制剂的高效力引起了人们对其可能对胎盘向胎儿供应雌激素的能力，进而对胎儿生长发育的影响的关注。
The personal care product Triclosan, 5-chloro-2(2,4-dichlorophenoxy)-phenol, is widely used in consumer products as an antibacterial agent and is increasingly found in the environment as a contaminant of sewage sludge and wastewater. This compound has been identified in plasma and urine of people in the United States, Sweden and Australia. Triclosan is known to inhibit sulfonation of phenolic xenobiotics and is structurally related to inhibitors of estrogen sulfotransferase, such as polychlorobiphenylols. In pregnancy, the placenta is an important source of estrogen, which is needed for normal fetal development and successful parturition, and estrogen sulfotransferase is thought to play an important role in regulation of estrogen availability. In this study, we examined the effect of Triclosan on sheep placental cytosolic sulfotransferase activity with 17-beta-estradiol and estrone as substrates. For comparison, we studied the effects of 4-hydroxy-3,3′,4′,5-tetrachlorobiphenyl and 2′-hydroxytriclocarban on estradiol sulfonation. The apparent Km for placental cytosolic sulfotransferase activity with estradiol as substrate was 0.27±0.06 nM (mean±S.D., n=3 individuals) and with estrone as substrate was 1.86±0.22 nM. Partial substrate inhibition was observed with estradiol at concentrations higher than 10–20 nM, as is typical of estrogen sulfotransferases (SULT1E1) in other species. Studies of the effect of Triclosan on estrogen sulfotransferase activity were conducted with several concentrations (0.1–6 nM) of estradiol and with 2 nM estrone. Triclosan was a very potent inhibitor of both estradiol and estrone sulfonation. For estradiol the inhibition was shown to be mixed competitive/uncompetitive, with Kic of 0.09±0.01 nM and Kiu of 5.2±2.9 nM. The IC50 for inhibition of estrone sulfonation was 0.60±0.06 nM. At an environmentally relevant concentration of 1 μM, Triclosan was not a substrate for glucuronidation in sheep placental microsomes. Triclosan could be sulfonated in placental cytosol with Km 1.14±0.18 μM and Vmax 160±26 pmol/min/mg protein, however the calculated rates of Triclosan sulfonation were negligible at the low nM concentrations that potently inhibit estrogen sulfonation. The high potency of Triclosan as an inhibitor of estrogen sulfotransferase activity raises concern about its possible effects on the ability of the placenta to supply estrogen to the fetus, and in turn on fetal growth and development.