TY - JOUR
T1 - Gene expression responses in male fathead minnows exposed to binary mixtures of an estrogen and antiestrogen
AU - Garcia-Reyero, Natàlia
AU - Kroll, Kevin J.
AU - Liu, Li
AU - Orlando, Edward F.
AU - Watanabe, Karen H.
AU - Sepúlveda, María S.
AU - Villeneuve, Daniel L.
AU - Perkins, Edward J.
AU - Ankley, Gerald T.
AU - Denslow, Nancy D.
N1 - Funding Information:
This work was supported by the Environmental Protection Agency STAR grant, (R831848) to ND, MS, EO and KW, and by a fellowship from the Spanish Ministry of Sciences and Technology (EX-2004-0986) co-funded by the European Union to NGR. We wish to thank Dr. Thomas Hutchinson, (formerly of AstraZeneca) for the generous gift of ZM189,154. The research described in this article does not necessarily reflect the views of the EPA and no official endorsement should be inferred. NDD holds equity in EcoArray, Inc., a company commercializing the microarray technology used in this study.
PY - 2009/7/13
Y1 - 2009/7/13
N2 - 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 17α-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 EE2/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 EE2 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 EE2/L or with the mixture of 5 ng EE2/L and 100 ng ZM 189,154/L indicated that some of the genes whose expression was changed by EE2 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. Conclusion: 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.
AB - 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 17α-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 EE2/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 EE2 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 EE2/L or with the mixture of 5 ng EE2/L and 100 ng ZM 189,154/L indicated that some of the genes whose expression was changed by EE2 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. Conclusion: 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.
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U2 - 10.1186/1471-2164-10-308
DO - 10.1186/1471-2164-10-308
M3 - Article
C2 - 19594897
AN - SCOPUS:67949095940
SN - 1471-2164
VL - 10
JO - BMC Genomics
JF - BMC Genomics
M1 - 308
ER -