Solak Kamila A, Wijnolts Fiona M J, Nijmeijer Sandra M, Blaauboer Bas J, van den Berg Martin, van Duursen Majorie B M
Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine Utrecht University, Yalelaan 104, 3584 CM Utrecht, The Netherlands.
Toxicol Rep. 2014 Jul 7;1:360-372. doi: 10.1016/j.toxrep.2014.06.006. eCollection 2014.
Phytoestrogens are plant-derived estrogen-like compounds that are increasingly used for their suggested health promoting properties, even by healthy, young women. However, scientific concerns exist regarding potential adverse effects on female reproduction. In this study, naringenin (NAR), 8-prenylnaringenin (8-PN), genistein (GEN), coumestrol (COU), quercetin (QUE) and resveratrol (RSV) up-regulated steroidogenic acute regulatory protein () mRNA levels in KGN human granulosa-like tumor cells. Most of the phytoestrogens tested also increased (aromatase) mRNA levels activation of ovary-specific and promoters. Yet, only NAR (3 and 10 μM), COU (10 and 30 μM) and QUE (10 μM) also statistically significantly induced aromatase activity in KGN cells after 24 h. 8-PN, aromatase inhibitor letrozole and estrogen receptor antagonist ICI 182,780 concentration-dependently inhibited aromatase activity with IC values of 8 nM, 10 nM and 72 nM, respectively. Co-exposure with ICI 182,780 (0.1 μM) statistically significantly attenuated the induction of aromatase activity by QUE and COU, but not NAR. Cell cycle status and proliferation of KGN cells were not affected by any of the phytoestrogens tested. Nonetheless, the migration of KGN cells was significantly reduced with approximately 30% by COU, RSV and QUE and 46% by GEN at 10 μM, but not NAR and 8-PN. Our results indicate that phytoestrogens can affect various pathways in granulosa-like cells at concentrations that can be found in plasma upon supplement intake. This implies that phytoestrogens may interfere with ovarian function and caution is in place regarding the use of supplements with high contents of phytoestrogens.
植物雌激素是一类源自植物的雌激素样化合物，因其具有潜在的促进健康特性而被越来越多的人使用，甚至包括健康的年轻女性。然而，对于其对女性生殖系统的潜在不良影响，科学界仍存在担忧。在本研究中，柚皮素（NAR）、8-异戊烯基柚皮素（8-PN）、染料木黄酮（GEN）、香豆雌酚（COU）、槲皮素（QUE）和白藜芦醇（RSV）上调了KGN人颗粒样肿瘤细胞中类固醇生成急性调节蛋白（）的mRNA水平。大多数测试的植物雌激素还增加了（芳香化酶）mRNA水平 卵巢特异性 和 启动子的激活。然而，仅NAR（3和10μM）、COU（10和30μM）和QUE（10μM）在24小时后在KGN细胞中也具有统计学意义地显著诱导芳香化酶活性。8-PN、芳香化酶抑制剂来曲唑和雌激素受体拮抗剂ICI 182,780浓度依赖性地抑制芳香化酶活性，IC值分别为8 nM、10 nM和72 nM。与ICI 182,780（0.1μM）共同暴露在统计学上显著减弱了QUE和COU对芳香化酶活性的诱导，但对NAR没有影响。所测试的任何植物雌激素均未影响KGN细胞的细胞周期状态和增殖。尽管如此，COU、RSV和QUE在10μM时可使KGN细胞的迁移显著减少约30%，GEN在10μM时可使其减少46%，但NAR和8-PN没有这种作用。我们的结果表明，植物雌激素可以在补充剂摄入后血浆中可检测到的浓度下影响颗粒样细胞中的各种途径。这意味着植物雌激素可能会干扰卵巢功能，对于高含量植物雌激素补充剂的使用需谨慎。
