Garcia-Reyero Natàlia, Barber David S, Gross Timothy S, Johnson Kevin G, Sepúlveda María S, Szabo Nancy J, Denslow Nancy D
Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, USA.
Aquat Toxicol. 2006 Jul 20;78(4):358-69. doi: 10.1016/j.aquatox.2006.05.003. Epub 2006 Jun 9.
Dieldrin and p,p'-DDE are ubiquitous contaminants known to act as endocrine disruptors, causing impaired development and reproduction in fish and wildlife. In order to elucidate the mechanisms by which dieldrin and p,p'-DDE cause endocrine disruption in largemouth bass (Micropterus salmoides), fish were exposed subchronically through the diet to both contaminants. Following 120 days of exposure, p,p'-DDE decreased estradiol in females, but increased 11-ketotestosterone in both sexes. Dieldrin on the other hand, decreased estradiol and 11-ketotestosterone in both sexes. Both pesticides also altered steady state mRNA expression levels of a set of genes chosen to represent three possible mechanisms of endocrine disruption: (1) direct interaction with soluble sex steroid receptors, (2) biosynthesis of endogenous sex hormones, and (3) metabolism of endogenous hormones. p,p'-DDE acted as a weak estrogen, increasing the expression of vitellogenin and estrogen receptor alpha in the liver. p,p'-DDE also altered the expression of genes involved in the synthesis of endogenous hormones as well as their metabolism. Dieldrin, on the other hand, only altered expression of vitellogenin and not estrogen receptor alpha. Dieldrin also altered the expression of genes involved in hormone synthesis and metabolism, and it dramatically lowered plasma hormone levels. Both pesticides targeted expression of genes involved in all three modes of action, suggesting that they each have multiple modes of action.
狄氏剂和p,p'-滴滴伊是普遍存在的污染物,已知它们作为内分泌干扰物,会导致鱼类和野生动物的发育和繁殖受损。为了阐明狄氏剂和p,p'-滴滴伊在大口黑鲈(Micropterus salmoides)中引起内分泌干扰的机制,通过饮食对鱼类进行亚慢性暴露于这两种污染物。暴露120天后,p,p'-滴滴伊降低了雌性中的雌二醇,但在两性中均增加了11-酮睾酮。另一方面,狄氏剂降低了两性中的雌二醇和11-酮睾酮。两种农药还改变了一组被选择用来代表内分泌干扰三种可能机制的基因的稳态mRNA表达水平:(1)与可溶性性类固醇受体的直接相互作用,(2)内源性性激素的生物合成,以及(3)内源性激素的代谢。p,p'-滴滴伊作为一种弱雌激素,增加了肝脏中卵黄蛋白原和雌激素受体α的表达。p,p'-滴滴伊还改变了参与内源性激素合成及其代谢的基因的表达。另一方面,狄氏剂仅改变了卵黄蛋白原的表达,而未改变雌激素受体α的表达。狄氏剂还改变了参与激素合成和代谢的基因的表达,并显著降低了血浆激素水平。两种农药都针对参与所有三种作用模式的基因的表达,表明它们各自具有多种作用模式。