Leaños-Castañeda Olga, van der Kraak Glen, Rodríguez-Canul Rossanna, Gold G
Department of Integrative Biology, University of Guelph, Ontario, Canada.
Toxicol Appl Pharmacol. 2007 Jun 1;221(2):158-67. doi: 10.1016/j.taap.2007.03.011. Epub 2007 Mar 23.
The aim of the present study was to evaluate, in vivo, the potential of o,p'-DDT to disrupt the endocrine system of mature male tilapia. In particular, the possibility that o,p'-DDT effects were mediated directly via the estrogen receptor (ER). Compounds with known ability to bind to the ER were employed: estradiol to induce and tamoxifen to inhibit the estrogenic effects result of the activation of the ER. In addition, an aromatase inhibitor, 4-hydrxyandrostenedione (4-OHA), was used to assess the ability of o,p'-DDT to induce estrogenic effects in a surrounding of low estradiol concentration. The effects of estradiol and o,p'-DDT were studied alone or in the presence of tamoxifen or 4-OHA at the end of a 12-day period of exposure. The main endpoints measured were plasma alkaline-labile phosphorous (ALP; an indirect indicator of vitellogenin), estradiol, testosterone and o,p'-DDT. It was found that o,p'-DDT was able to induce the vitellogenesis (measured as plasma ALP increase) and decrease the circulating levels of estradiol and testosterone. Interestingly, o,p'-DDT kept this ability in whole fish with low concentrations of estradiol which would exclude endogenous estradiol as indirect mediator of the estrogenic effects induced by o,p'-DDT. In addition, the plasma concentration of o,p'-DDT, instead of that of estradiol, was closely related to the plasma ALP increase induced by o,p'-DDT. This indicates that o,p'-DDT could have directly activated the vitellogenesis. The antiestrogenic action of tamoxifen to inhibit the vitellogenesis and the decrease on plasma estradiol induced by o,p'-DDT indicates that o,p'-DDT can bind directly to the ER. In conclusion, this in vivo study shows that o,p'-DDT has the potential to disrupt the endocrine system and strongly supports that the estrogenic actions of o,p'-DDT involve binding to the ER.
本研究的目的是在体内评估o,p'-滴滴涕破坏成熟雄性罗非鱼内分泌系统的可能性。特别是，o,p'-滴滴涕的作用是否直接通过雌激素受体（ER）介导。使用了已知能与ER结合的化合物：雌二醇用于诱导，他莫昔芬用于抑制ER激活产生的雌激素效应。此外，一种芳香化酶抑制剂4-羟基雄烯二酮（4-OHA）用于评估o,p'-滴滴涕在低雌二醇浓度环境中诱导雌激素效应的能力。在暴露12天结束时，单独或在他莫昔芬或4-OHA存在的情况下研究了雌二醇和o,p'-滴滴涕的作用。测量的主要终点是血浆碱性不稳定磷（ALP；卵黄蛋白原的间接指标）、雌二醇、睾酮和o,p'-滴滴涕。研究发现，o,p'-滴滴涕能够诱导卵黄生成（以血浆ALP升高衡量），并降低雌二醇和睾酮的循环水平。有趣的是，o,p'-滴滴涕在低雌二醇浓度的整条鱼中仍保持这种能力，这将排除内源性雌二醇作为o,p'-滴滴涕诱导的雌激素效应的间接介质。此外，o,p'-滴滴涕的血浆浓度而非雌二醇的血浆浓度与o,p'-滴滴涕诱导的血浆ALP升高密切相关。这表明o,p'-滴滴涕可能直接激活了卵黄生成。他莫昔芬抑制卵黄生成的抗雌激素作用以及对o,p'-滴滴涕诱导的血浆雌二醇降低表明o,p'-滴滴涕可以直接与ER结合。总之，这项体内研究表明o,p'-滴滴涕有破坏内分泌系统的潜力，并有力地支持了o,p'-滴滴涕的雌激素作用涉及与ER结合。
