Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.
Toxicol In Vitro. 2012 Oct;26(7):1114-21. doi: 10.1016/j.tiv.2012.06.016. Epub 2012 Jul 5.
Nonylphenol (NP) has been proven to be one of the most investigated xenohormones interacting with the estrogen receptor. Technical nonylphenol (t-NP) contains at least 20 para-substituted isomers. It has been shown that NP isomers vary in their estrogenic potency. So the use of mixtures or impure substances can lead to misinterpretations and unsatisfying conclusions. In the present study, experiments were performed to examine effects of NP isomers on steroidogenesis of rat Leydig cells. Primary cultured Leydig cells were exposed to NP isomers (p33-NP, p262-NP, p353-NP, p363-NP) at the optimized inhibitory concentration 5μmol/L for 6h. NP isomers showed various degrees of inhibition of testosterone biosynthesis, with p363-NP leading to the most significant decrease and others sharing the similar efficacy. The expression of 3b-HSD, Cyp11a1, Star and the apoptosis of Leydig cells were further measured to investigate the underlying mechanisms. We demonstrated that NP isomers can affect the steroidogenesis of rat Leydig cells, at least in part, through their influence on gene expression and cell apoptosis, but varied in their individual degree. However, the final results were not completely coincident with their estrogenic potency tested in vitro, which implies that effects of NP isomers on steroidogenesis appear to be mediated through some other underlying mechanisms besides their various estrogenic potency.
壬基酚 (NP) 已被证明是与雌激素受体相互作用的最受研究的外源性激素之一。技术壬基酚 (t-NP) 含有至少 20 种对位取代的同分异构体。已经表明,NP 异构体在雌激素活性方面存在差异。因此,使用混合物或不纯物质可能会导致误解和不满意的结论。在本研究中,进行了实验来研究 NP 异构体对大鼠睾丸间质细胞类固醇生成的影响。原代培养的睾丸间质细胞在优化的抑制浓度 5μmol/L 下暴露于 NP 异构体 (p33-NP、p262-NP、p353-NP、p363-NP) 6h。NP 异构体对睾酮生物合成表现出不同程度的抑制作用,其中 p363-NP 导致的抑制作用最为显著,其他异构体的抑制作用相似。进一步测量 3b-HSD、Cyp11a1、Star 的表达和睾丸间质细胞的凋亡,以研究其潜在机制。我们证明,NP 异构体可以通过影响基因表达和细胞凋亡来影响大鼠睾丸间质细胞的类固醇生成,至少在一定程度上如此,但它们的个体程度不同。然而,最终结果与它们在体外测试的雌激素活性不完全一致,这意味着 NP 异构体对类固醇生成的影响似乎是通过除雌激素活性以外的其他潜在机制介导的。