Ruggeri B, Ubaldi M, Lourdusamy A, Soverchia L, Ciccocioppo R, Hardiman G, Baker M E, Palermo F, Polzonetti-Magni A M
Department of Experimental Medicine and Public Health, University of Camerino, via Madonna delle Carceri, 62032 Camerino (MC), Italy.
Gen Comp Endocrinol. 2008 Aug;158(1):138-44. doi: 10.1016/j.ygcen.2008.05.012. Epub 2008 May 29.
There is much concern about the increasing presence in the environment of synthetic chemicals that are able to disrupt the endocrine system. Among these compounds, 4-nonylphenol (4-NP) is one of the most studied xenoestrogens, due to its widespread accumulation in water sediment and consequent presence in fatty acid of aquatic organisms. Here, we have used a zebrafish microarray representing 16,399 genes to study the effects of 4-NP and estradiol-17beta (E2) in adult male zebrafish in order to elucidate the mechanism of action of 4-NP compared with that of E2. The microarray results showed that both 4-NP and E2 induced a strong expression of vitellogenin (VTG), the sex related precursor of the yolk proteins in oviparous vertebrates. Both treatments induced elevated protein turnover upregulating genes involved in proteolysis and those that are constituents of the ribosome. Many genes regulated by 4-NP and E2 are involved in energy metabolism, oxidative stress defense mechanisms, xenobiotic metabolism, and lipid metabolism. A different pattern of expression in the two treatments was found for genes involved in oxidative stress, since E2 seems to induce the mechanism of detoxification, while 4-NP seems to inhibit this protective mechanism of the cell. Overall, these findings demonstrate that the microarray approach can contribute significantly to the understanding of expression patterns induced by E2 and 4-NP in male zebrafish. The results also demonstrate that 4-NP is able to act through an alternative pattern to that of estradiol-17beta, modulating the expression of the same genes in a different manner.
人们对环境中日益增多的能够干扰内分泌系统的合成化学物质深感担忧。在这些化合物中,4-壬基酚(4-NP)是研究最多的外源性雌激素之一,因为它在水沉积物中广泛积累,并因此存在于水生生物的脂肪酸中。在此,我们使用了一个代表16399个基因的斑马鱼微阵列,来研究4-NP和17β-雌二醇(E2)对成年雄性斑马鱼的影响,以便阐明4-NP与E2相比的作用机制。微阵列结果表明,4-NP和E2均诱导了卵黄蛋白原(VTG)的强烈表达,VTG是卵生脊椎动物中与性别相关的卵黄蛋白前体。两种处理均诱导蛋白质周转率升高,上调了参与蛋白水解的基因以及核糖体的组成基因。许多受4-NP和E2调控的基因参与能量代谢、氧化应激防御机制、外源性物质代谢和脂质代谢。对于参与氧化应激的基因,在两种处理中发现了不同的表达模式,因为E2似乎诱导解毒机制,而4-NP似乎抑制细胞的这种保护机制。总体而言,这些发现表明微阵列方法能够显著有助于理解E2和4-NP在雄性斑马鱼中诱导的表达模式。结果还表明,4-NP能够通过一种不同于17β-雌二醇的模式起作用,以不同方式调节相同基因的表达。