title: Methoxychlor affects multiple hormone signaling pathways in the largemouth bass (Micropterus salmoides) liver.
abstract: Methoxychlor (MXC) is an organochlorine pesticide that has been shown to have estrogenic activity by activating estrogen receptors and inducing vitellogenin production in male fish. Previous studies report that exposure to MXC induces changes in mRNA abundance of reproductive genes in the liver and testes of largemouth bass (Micropterus salmoides). The objective of the present study was to better characterize the mode of action of MXC by measuring the global transcriptomic response in the male largemouth liver using an oligonucleotide microarray. Microarray analysis identified highly significant changes in the expression of 37 transcripts (p<0.001) (20 induced and 17 decreased) in the liver after MXC injection and a total of 900 expression changes (p<0.05) in transcripts with high homology to known genes. Largemouth bass estrogen receptor alpha (esr1) and androgen receptor (ar) were among the transcripts that were increased in the liver after MXC treatment. Functional enrichment analysis identified the molecular functions of steroid binding and androgen receptor activity as well as steroid hormone receptor activity as being significantly over-represented gene ontology terms. Pathway analysis identified c-fos signaling as being putatively affected through both estrogen and androgen signaling. This study provides evidence that MXC elicits transcriptional effects through the estrogen receptor as well as androgen receptor-mediated pathways in the liver.
authors.affiliation: Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611-0885, USA. cmartyn@unb.ca
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martyniuk
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Spade
authors.forename: Jason L
authors.initials: JL
authors.lastname: Blum
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Kroll
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Denslow
mesh_terms: D000818:Animals; D001492:Bass / Q000502:physiology*; D016000:Cluster Analysis; D017931:DNA Primers / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008731:Methoxychlor / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D043922:Toxicogenetics
chemical_list: D017931:DNA Primers; D047628:Estrogen Receptor alpha; D007306:Insecticides; D016760:Proto-Oncogene Proteins c-fos; D011944:Receptors, Androgen; D008731:Methoxychlor