Yadetie F, Arukwe A, Goksøyr A, Male R
Department of Molecular Biology, University of Bergen, Norway.
Sci Total Environ. 1999 Aug 15;233(1-3):201-10. doi: 10.1016/s0048-9697(99)00226-0.
Alkylphenol ethoxylate degradation products such as nonylphenol and octylphenol are shown to have estrogenic effects. Nonylphenol induces synthesis of vitellogenin (a precursor of egg yolk proteins) and zona radiata proteins (eggshell proteins) in juvenile and/or male fish. Little is known about the molecular mechanisms of estrogenicity of environmental chemicals such as nonylphenol. To study the mechanisms of estrogenic effects of 4-nonylphenol (NP), we examined its in vivo effects on the expression of the estrogen receptor (ER), vitellogenin (Vtg) and zona radiata protein (Zrp) genes in juvenile Atlantic salmon liver. We show that the ER mRNA synthesis is induced by NP in a dose-dependent manner in juvenile Atlantic salmon liver. The induction of the ER mRNA synthesis is followed by the induction of Zrp and Vtg mRNA synthesis. The ER transcripts reach peak levels earlier than the Zrp and Vtg mRNA and proteins, which is in agreement with the physiological effects of estradiol during zonagenesis and vitellogenesis. Various studies have also shown that NP competitively inhibits the binding of 17 beta-estradiol (E2) to ER. Our results further suggest that NP directly mimics E2 in inducing the ER, Zrp and Vtg genes in salmon liver.
烷基酚聚氧乙烯醚降解产物,如壬基酚和辛基酚,已被证明具有雌激素效应。壬基酚可诱导幼鱼和/或雄鱼合成卵黄蛋白原(一种蛋黄蛋白前体)和放射带蛋白(蛋壳蛋白)。对于壬基酚等环境化学物质的雌激素作用分子机制,人们了解甚少。为研究4-壬基酚(NP)的雌激素效应机制,我们检测了其对幼年大西洋鲑鱼肝中雌激素受体(ER)、卵黄蛋白原(Vtg)和放射带蛋白(Zrp)基因表达的体内影响。我们发现,NP可在幼年大西洋鲑鱼肝中以剂量依赖方式诱导ER mRNA合成。ER mRNA合成的诱导之后是Zrp和Vtg mRNA合成的诱导。ER转录本达到峰值水平的时间早于Zrp和Vtg mRNA及蛋白质,这与雌二醇在卵膜形成和卵黄生成过程中的生理作用一致。各种研究还表明,NP可竞争性抑制17β-雌二醇(E2)与ER的结合。我们的结果进一步表明,NP在诱导鲑鱼肝中的ER、Zrp和Vtg基因方面直接模拟了E2。