Parabens inhibit human skin estrogen sulfotransferase activity: Possible link to paraben estrogenic effects
Parabens inhibit human skin estrogen sulfotransferase activity: Possible link to paraben estrogenic effects
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DOI：
10.1016/j.tox.2007.01.010
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发表时间：
2007-04-11
期刊：
影响因子：
4.5
通讯作者：
Voorman, Richard L.
中科院分区：
文献类型：
--
作者：
Prusakiewicz, Jeffery J.;Harville, Heather A.;Voorman, Richard L.
对羟基苯甲酸酯（对羟基苯甲酸酯）是一组广泛用于局部化妆品和药品中的防腐剂。对羟基苯甲酸酯在体外或基于细胞的模型中与雌激素受体表现出弱关联，但在动物模型中确实表现出雌激素作用。我们的假设是，对羟基苯甲酸酯发挥雌激素作用的部分原因是通过抑制皮肤中的雌激素磺基转移酶 (SULT) 来提高雌激素水平。我们在这里报告了对羟基苯甲酸酯作为人皮肤细胞质部分和正常人表皮角质形成细胞中雌激素硫酸化抑制剂的结构-活性-关系的结果。与对羟基苯甲酸酯雌激素性和雌激素受体亲和力的报道类似，SULT 抑制的效力随着对羟基苯甲酸酯链长度的增加而增加。研究发现，对羟基苯甲酸丁酯是皮肤细胞质中最有效的对羟基苯甲酸酯，其 IC50 值为 37 +/- 5 μM。对羟基苯甲酸丁酯可阻断雌二醇和雌酮的皮肤细胞质硫酸化，但不能阻断雄激素脱氢表雄酮。还在正常人表皮角质形成细胞的细胞系统中测试了对羟基苯甲酸酯作为 SULT 活性抑制剂的作用。相对于皮肤细胞质的 IC50 值，对羟基苯甲酸丁酯在这些细胞中的效力增加了三倍。总体而言，这些结果表明，长期局部使用对羟基苯甲酸酯可能会因抑制雌激素磺基转移酶活性而导致皮肤中雌激素作用延长。因此，许多外用化妆品和药物的皮肤抗衰老功效可能部分源自对羟基苯甲酸酯的雌激素作用。 (c) 2007 Elsevier Ireland Ltd. 保留所有权利。
Parabens (p-hydroxybenzoate esters) are a group of widely used preservatives in topically applied cosmetic and pharmaceutical products. Parabens display weak associations with the estrogen receptors in vitro or in cell based models, but do exhibit estrogenic effects in animal models. It is our hypothesis that parabens exert their estrogenic effects, in part, by elevating levels of estrogens through inhibition of estrogen sulfotransferases (SULTs) in skin. We report here the results of a structure-activity-relationship of parabens as inhibitors of estrogen sulfation in human skin cytosolic fractions and normal human epidermal keratinocytes. Similar to reports of paraben estrogenicity and estrogen receptor affinity, the potency of SULT inhibition increased as the paraben ester chain length increased. Butylparaben was found to be the most potent of the parabens in skin cytosol, yielding an IC50 value of 37 +/- 5 mu M. Butylparaben blocked the skin cytosol sulfation of estradiol and estrone, but not the androgen dehydroepiandrosterone. The parabens were also tested as inhibitors of SULT activity in a cellular system, with normal human epidermal keratinocytes. The potency of butylparaben increased three-fold in these cells relative to the IC50 value from skin cytosol. Overall, these results suggest chronic topical application of parabens may lead to prolonged estrogenic effects in skin as a result of inhibition of estrogen sulfotransferase activity. Accordingly, the skin anti-aging benefits of many topical cosmetics and pharmaceuticals could be derived, in part, from the estrogenicity of parabens. (c) 2007 Elsevier Ireland Ltd. All rights reserved.