Estrogen-responsive gene networks in the teleost liver: What are the key molecular indicators?

The objective of this study was to identify core groups of transcripts and molecular signaling pathways that respond to 17alpha-ethylinestadiol (EE2), a ubiquitous estrogenic contaminant, using transcriptome datasets generated from six independent laboratories. We sought to determine which biomarkers and gene networks were those most robust and reliably detected in multiple laboratories. Six laboratories conducted microarray analysis in pieces of the same liver from male fathead minnows exposed to ∼15ng/L EE2 for 96hours. There were common transcriptional networks identified in every dataset. These included a down-regulation of gene networks associated with blood clotting, complement activation, triglyceride storage, and xenobiotic metabolism. Noteworthy was that more than ∼85% of the gene networks were suppressed by EE2. Leveraging both these data and those mined from the Comparative Toxicogenomics Database (CTD), we narrowed in on an EE2-responsive transcriptional network. All transcripts in this network responded ∼±5-fold or more to EE2, increasing reliability of detection. This network included estrogen receptor alpha, transferrin, myeloid cell leukemia 1, insulin like growth factor 1, insulin like growth factor binding protein 2, and methionine adenosyltransferase 2A. This estrogen-responsive interactome has the advantage over single markers (e.g. vitellogenin) in that these entities are directly connected to each other based upon evidence of expression regulation...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research