Taxvig Camilla, Vinggaard Anne Marie, Hass Ulla, Axelstad Marta, Boberg Julie, Hansen Pernille Reimer, Frederiksen Hanne, Nellemann Christine
National Food Institute, Technical University of Denmark, Department of Toxicology and Risk Assessment, DK-2860 Søborg, Denmark.
Toxicol Sci. 2008 Nov;106(1):206-13. doi: 10.1093/toxsci/kfn148. Epub 2008 Jul 22.
The effects of ethyl and butyl paraben on steroidogenesis were evaluated in rats exposed in utero. Pregnant Wistar rats were dosed from gestational day (GD) 7 to GD 21, followed by examination of the dams, and the fetuses. Additionally, both parabens were tested in vitro in the H295R steroidogenesis assay and in the T-screen assay, the later to test for their ability to act as thyroid hormone receptor agonist or antagonist. In the in utero exposure toxicity study, neither ethyl nor butyl paraben showed any treatment-related effects on testosterone production, anogenital distance, or testicular histopathology. However, butyl paraben caused a significant decrease in the mRNA expression level of estradiol receptor-beta in fetal ovaries, and also significantly decreased the mRNA expression of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the adrenal glands. In vitro butyl paraben increased the proliferation of the GH3 cells in the T-Screen assay, thereby acting as a weak thyroid hormone receptor agonist. In the adrenal H295R steroidogenesis assay both ethyl and butyl paraben caused a significant increase in the progesterone formation. Overall, the results indicate that butyl paraben might have the ability to act as endocrine disruptor by interfering with the transport of cholesterol to the mitochondrion, thereby interfering with steroidogenesis, but also that the two tested parabens do not show clear endocrine disrupting capabilities in our short-term in vivo experiment.
在子宫内暴露的大鼠中评估了对羟基苯甲酸乙酯和对羟基苯甲酸丁酯对类固醇生成的影响。将怀孕的Wistar大鼠从妊娠第7天(GD)至第21天给药,随后检查母鼠和胎儿。此外,两种对羟基苯甲酸酯在H295R类固醇生成试验和T-筛选试验中进行了体外测试,后者用于测试它们作为甲状腺激素受体激动剂或拮抗剂的能力。在子宫内暴露毒性研究中,对羟基苯甲酸乙酯和对羟基苯甲酸丁酯均未显示出对睾酮生成、肛殖距或睾丸组织病理学有任何与治疗相关的影响。然而,对羟基苯甲酸丁酯导致胎儿卵巢中雌二醇受体-β的mRNA表达水平显著降低,并且还显著降低了肾上腺中类固醇生成急性调节蛋白和外周苯二氮䓬受体的mRNA表达。在体外,在T-筛选试验中对羟基苯甲酸丁酯增加了GH3细胞的增殖,从而作为一种弱甲状腺激素受体激动剂。在肾上腺H295R类固醇生成试验中,对羟基苯甲酸乙酯和对羟基苯甲酸丁酯均导致孕酮生成显著增加。总体而言,结果表明对羟基苯甲酸丁酯可能具有通过干扰胆固醇向线粒体的转运来充当内分泌干扰物的能力,从而干扰类固醇生成,但在我们的短期体内实验中,这两种测试的对羟基苯甲酸酯并未显示出明显的内分泌干扰能力。