Parabens are commonly used preservatives in cosmetics, food, and pharmaceutical products. The objective of this study was to examine the effect of nine parabens on human and rat 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) in human placental and rat ovarian cytosols, as well as on estradiol synthesis in BeWo cells. The results showed that the IC values for these compounds varied from methylparaben with the weakest inhibition (106.42 μM) to hexylparaben with the strongest inhibition (2.05 μM) on human 17β-HSD1. Mode action analysis revealed that these compounds acted as mixed inhibitors. For rats, the IC values ranged from the weakest inhibition for methylparaben (no inhibition at 100 μM) to the most potent inhibition for hexylparaben (0.87 μM), and they functioned as mixed inhibitors. Docking analysis indicated that parabens bind to the region bridging the NADPH and steroid binding sites of human 17β-HSD1 and the NADPH binding site of rat 17β-HSD1. Bivariate correlation analysis demonstrated negative correlations between LogP, molecular weight, heavy atoms, and apolar desolvation energy, and the IC values of these compounds. In conclusion, this study identified the inhibitory effects of parabens and their binding mechanisms on human and rat 17β-HSD1, as well as their impact on hormone synthesis.

中文翻译：

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对羟基苯甲酸酯对人和大鼠 17β-羟基类固醇脱氢酶的抑制作用 1：作用机制及其对激素合成的影响


对羟基苯甲酸酯是化妆品、食品和药品中常用的防腐剂。本研究的目的是检测九种对羟基苯甲酸酯对人和大鼠胎盘和大鼠卵巢细胞质中的 17β-羟基类固醇脱氢酶 1 (17β-HSD1) 以及 BeWo 细胞中雌二醇合成的影响。结果表明，这些化合物的 IC 值从对人 17β-HSD1 抑制最弱的对羟基苯甲酸甲酯 (106.42 μM) 到对人 17β-HSD1 抑制最强的对羟基苯甲酸己酯 (2.05 μM)。模式作用分析表明这些化合物充当混合抑制剂。对于大鼠，IC50 值范围从对羟基苯甲酸甲酯的最弱抑制（100 μM 无抑制）到对羟基苯甲酸己酯的最强抑制（0.87 μM），并且它们起到混合抑制剂的作用。对接分析表明，对羟基苯甲酸酯类与桥接人 17β-HSD1 的 NADPH 和类固醇结合位点以及大鼠 17β-HSD1 的 NADPH 结合位点的区域结合。双变量相关分析表明 LogP、分子量、重原子和非极性去溶剂化能与这些化合物的 IC 值之间呈负相关。总之，本研究确定了对羟基苯甲酸酯的抑制作用及其对人和大鼠 17β-HSD1 的结合机制，以及它们对激素合成的影响。