Centre for Arctic Health and Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Building 1260, Bartholins Allé 2, 8000, Aarhus, Denmark.
Environ Sci Pollut Res Int. 2013 Nov;20(11):8031-44. doi: 10.1007/s11356-013-1753-3. Epub 2013 Jun 14.
Perfluorinated compounds (PFCs) are a large group of chemicals used in different industrial and commercial applications. Studies have suggested the potential of some PFCs to disrupt endocrine homeostasis, increasing the risk of adverse health effects. This study aimed to elucidate mechanisms behind PFC interference with steroid hormone receptor functions. Seven PFCs [perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA)] were analyzed in vitro for their potential to affect estrogen receptor (ER) and androgen receptor (AR) transactivity as well as aromatase enzyme activity. The PFCs were assessed as single compounds and in an equimolar mixture. PFHxS, PFOS and PFOA significantly induced the ER transactivity, whereas PFHxS, PFOS, PFOA, PFNA and PFDA significantly antagonized the AR activity in a concentration-dependent manner. Moreover, PFDA weakly decreased the aromatase activity at a high test concentration. A mixture effect more than additive was observed on AR function. We conclude that five of the seven PFCs possess the potential in vitro to interfere with the function of the ER and/or the AR. The observed mixture effect emphasizes the importance of considering the combined action of PFCs in future studies to assess related health risks.
全氟化合物(PFCs)是一大类用于不同工业和商业应用的化学物质。研究表明,一些 PFCs 具有破坏内分泌稳态的潜力,增加了不良健康影响的风险。本研究旨在阐明 PFC 干扰甾体激素受体功能的机制。七种 PFCs [全氟己烷磺酸(PFHxS)、全氟辛烷磺酸(PFOS)、全氟辛酸(PFOA)、全氟壬酸(PFNA)、全氟癸酸(PFDA)、全氟十一烷酸(PFUnA)和全氟十二烷酸(PFDoA)] 被分析了其潜在的影响雌激素受体(ER)和雄激素受体(AR)转录活性以及芳香酶酶活性的能力。这些 PFCs 被评估为单一化合物和等摩尔混合物。PFHxS、PFOS 和 PFOA 显著诱导 ER 转录活性,而 PFHxS、PFOS、PFOA、PFNA 和 PFDA 则以浓度依赖的方式显著拮抗 AR 活性。此外,PFDA 在高测试浓度下弱地降低芳香酶活性。在 AR 功能上观察到混合物效应大于加性。我们得出结论,七种 PFCs 中有五种具有体外干扰 ER 和/或 AR 功能的潜力。观察到的混合物效应强调了在未来研究中考虑 PFC 联合作用以评估相关健康风险的重要性。