Expression signatures for a model androgen and antiandrogen in the fathead minnow (Pimephales promelas) ovary

Natália Garcia-Reyero, Daniel L. Villeneuve, Kevin J. Kroll, Li Liu, Edward F. Orlando, Karen H. Watanabe, María S. Sepulveda, Gerald T. Ankley, Nancy D. Denslow

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Trenbolone, an anabolic androgen, and flutamide, an antiandrogen, are prototypical model compounds for agonism and antagonism of the androgen receptor. We hypothesized that 48 h exposures of female fathead minnows (Pimephales promelas) to environmentally relevant concentrations of these chemicals would alter genes regulated by the androgen receptor and that a mixture of the two compounds would block the effects. Gene expression in the ovaries was analyzed using a fathead minnow-specific 22 000-gene microarray. Flutamide altered about twice the number of genes as trenbolone, most of which appeared to be through pathways not associated with the androgen receptor. A group of 70 genes, of which we could identify 37, were reciprocally regulated by trenbolone and flutamide. These are candidates for specific biomarkers for androgen receptor mediated gene expression. Four genes stand out as specifically related to reproduction: sperm associated antigen 8 (SPAG8), CASP8 and FADD-like apoptosis regulator (CFLAR), corticotropin releasing hormone (CRH), and 3β-hydroxysteroid dehydrogenases (3β-HSD). Three notable transcriptional regulators including myelocytomatosis viral oncogene homologue (MYC), Yin Yang 1 (YY1), and interferon regulator factor 1 (IRF1) may function as early molecular switches to control phenotypic changes in ovary tissue architecture and function in response to androgen or antiandrogen exposure.

Original languageEnglish (US)
Pages (from-to)2614-2619
Number of pages6
JournalEnvironmental Science and Technology
Volume43
Issue number7
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Environmental Chemistry

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    Garcia-Reyero, N., Villeneuve, D. L., Kroll, K. J., Liu, L., Orlando, E. F., Watanabe, K. H., Sepulveda, M. S., Ankley, G. T., & Denslow, N. D. (2009). Expression signatures for a model androgen and antiandrogen in the fathead minnow (Pimephales promelas) ovary. Environmental Science and Technology, 43(7), 2614-2619. https://doi.org/10.1021/es8024484