title: Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen.
abstract: BACKGROUND
  Aquatic organisms are continuously exposed to complex mixtures of chemicals, many of which can interfere with their endocrine system, resulting in impaired reproduction, development or survival, among others. In order to analyze the effects and mechanisms of action of estrogen/anti-estrogen mixtures, we exposed male fathead minnows (Pimephales promelas) for 48 hours via the water to 2, 5, 10, and 50 ng 17alpha-ethinylestradiol (EE2)/L, 100 ng ZM 189,154/L (a potent antiestrogen known to block activity of estrogen receptors) or mixtures of 5 or 50 ng EE(2)/L with 100 ng ZM 189,154/L. We analyzed gene expression changes in the gonad, as well as hormone and vitellogenin plasma levels.
  
  
  RESULTS
  Steroidogenesis was down-regulated by EE(2) as reflected by the reduced plasma levels of testosterone in the exposed fish and down-regulation of genes in the steroidogenic pathway. Microarray analysis of testis of fathead minnows treated with 5 ng EE(2)/L or with the mixture of 5 ng EE(2)/L and 100 ng ZM 189,154/L indicated that some of the genes whose expression was changed by EE(2) were blocked by ZM 189,154, while others were either not blocked or enhanced by the mixture, generating two distinct expression patterns. Gene ontology and pathway analysis programs were used to determine categories of genes for each expression pattern.
  
  
  CONCLUSIONS
  Our results suggest that response to estrogens occurs via multiple mechanisms, including canonical binding to soluble estrogen receptors, membrane estrogen receptors, and other mechanisms that are not blocked by pure antiestrogens.
authors: Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA. natalia@ccmsi.us
authors: Natàlia
authors: N
authors: Garcia-Reyero
authors: Kevin J
authors: KJ
authors: Kroll
authors: Li
authors: L
authors: Liu
authors: Edward F
authors: EF
authors: Orlando
authors: Karen H
authors: KH
authors: Watanabe
authors: María S
authors: MS
authors: Sepúlveda
authors: Daniel L
authors: DL
authors: Villeneuve
authors: Edward J
authors: EJ
authors: Perkins
authors: Gerald T
authors: GT
authors: Ankley
authors: Nancy D
authors: ND
authors: Denslow
mesh_terms: D000818:Animals; D003530:Cyprinidae / Q000235:genetics* / Q000502:physiology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014819:Vitellogenins / Q000097:blood
chemical_list: D020847:Estrogen Receptor Modulators; D004967:Estrogens; D014819:Vitellogenins; D013739:Testosterone; D004997:Ethinyl Estradiol