Interference of Paraben Compounds with Estrogen Metabolism by Inhibition of 17β-Hydroxysteroid Dehydrogenases.
Interference of Paraben Compounds with Estrogen Metabolism by Inhibition of 17β-Hydroxysteroid Dehydrogenases.
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DOI：
10.3390/ijms18092007
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发表时间：
2017-09-19
影响因子：
5.6
通讯作者：
Odermatt A
中科院分区：
文献类型：
--
作者：
Engeli RT;Rohrer SR;Vuorinen A;Herdlinger S;Kaserer T;Leugger S;Schuster D;Odermatt A
对羟基苯甲酸酯是有效的防腐剂，广泛用于化妆品和加工食品，人类接触量很高。最近的证据表明对羟基苯甲酸酯具有雌激素作用。这项工作研究了对羟基苯甲酸酯对雌激素激活酶 17β-羟基类固醇脱氢酶 (17β-HSD) 1 和雌激素失活 17β-HSD2 的潜在干扰。应用基于配体的 17β-HSD2 药效团模型来筛选化妆品化学品数据库，然后体外测试选定的对羟基苯甲酸酯化合物对 17β-HSD1 和 17β-HSD2 活性的抑制作用。除常见代谢物对羟基苯甲酸外，所有测试的对羟基苯甲酸酯和对羟基苯甲酸酯类化合物均抑制 17β-HSD2。对羟基苯甲酸乙酯和香草酸乙酯抑制 17β-HSD2，IC50 值分别为 4.6 ± 0.8 和 1.3 ± 0.3 µM。此外，对羟基苯甲酸酯大小依赖性地抑制 17β-HSD1，其中对羟基苯甲酸己酯和庚基苯甲酸酯的活性最强，IC50 值为 2.6 ± 0.6 和 1.8 ± 0.3 µM。低微摩尔浓度的对羟基苯甲酸己酯和对羟基苯甲酸庚酯可降低 17β-HSD1 活性，对羟基苯甲酸乙酯和香草酸乙酯可降低 17β-HSD2 活性。然而，考虑到这些化合物通过酯酶非常快速地代谢为无活性的对羟基苯甲酸，需要确定在什么条件下这些对羟基苯甲酸酯或其混合物可以在靶细胞中出现低微摩尔浓度，以有效干扰体内雌激素作用。
Parabens are effective preservatives widely used in cosmetic products and processed food, with high human exposure. Recent evidence suggests that parabens exert estrogenic effects. This work investigated the potential interference of parabens with the estrogen-activating enzyme 17β-hydroxysteroid dehydrogenase (17β-HSD) 1 and the estrogen-inactivating 17β-HSD2. A ligand-based 17β-HSD2 pharmacophore model was applied to screen a cosmetic chemicals database, followed by in vitro testing of selected paraben compounds for inhibition of 17β-HSD1 and 17β-HSD2 activities. All tested parabens and paraben-like compounds, except their common metabolite p-hydroxybenzoic acid, inhibited 17β-HSD2. Ethylparaben and ethyl vanillate inhibited 17β-HSD2 with IC50 values of 4.6 ± 0.8 and 1.3 ± 0.3 µM, respectively. Additionally, parabens size-dependently inhibited 17β-HSD1, whereby hexyl- and heptylparaben were most active with IC50 values of 2.6 ± 0.6 and 1.8 ± 0.3 µM. Low micromolar concentrations of hexyl- and heptylparaben decreased 17β-HSD1 activity, and ethylparaben and ethyl vanillate decreased 17β-HSD2 activity. However, regarding the very rapid metabolism of these compounds to the inactive p-hydroxybenzoic acid by esterases, it needs to be determined under which conditions low micromolar concentrations of these parabens or their mixtures can occur in target cells to effectively disturb estrogen effects in vivo.
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影响因子：
12.3
作者：
Lin CY;Ström A;Vega VB;Kong SL;Yeo AL;Thomsen JS;Chan WC;Doray B;Bangarusamy DK;Ramasamy A;Vergara LA;Tang S;Chong A;Bajic VB;Miller LD;Gustafsson JA;Liu ET
通讯作者：
Liu ET
影响因子：
14.9
作者：
Kim S;Thiessen PA;Bolton EE;Chen J;Fu G;Gindulyte A;Han L;He J;He S;Shoemaker BA;Wang J;Yu B;Zhang J;Bryant SH
通讯作者：
Bryant SH
影响因子：
3.8
作者：
Routledge, EJ;Parker, J;Sumpter, JP
通讯作者：
Sumpter, JP
DOI：
10.1038/jes.2011.22
发表时间：
2011-11-01
影响因子：
4.5
作者：
Sandanger, Torkjel M.;Huber, Sandra;Lund, Eiliv
通讯作者：
Lund, Eiliv
影响因子：
8.8
作者：
Gunnarsson, C;Hellqvist, E;Stål, O
通讯作者：
Stål, O