Fathead minnow ovaries exposed in vivo or in vitro to fadrozole
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ABSTRACT: Interpreting proteomic and genomic data is a major challenge in predictive ecotoxicology that can be addressed by a systems biology approach. Mathematical modeling provides an organizational platform to consolidate protein dynamics with possible genomic regulation. Here, a model of ovarian steroidogenesis in the fathead minnow (Pimephales promelas) is developed to evaluate possible transcriptional regulation of the steroid production observed in microarray studies. Steroidogenesis, the production of sex steroids, is a highly conserved pathway whose regulation is critical to sexual reproduction. The model was developed from literature sources, integrating key signaling components (G-protein and PKA activation) with their ensuing effect on steroid production. The model properly predicted steroid behavior when fish were exposed to fadrozole, a specific aromatase inhibitor, but failed to predict testosterone and estradiol behavior during depuration. In vivo microarray data implicated three modes of regulation which may account for over-production of steroids during depuration: P450 enzyme up-regulation, inhibin down-regulation, or luteinizing hormone up-regulation. Simulation studies and sensitivity analysis were used to evaluate each of the three modes as possible sources of compensation.
ORGANISM(S): Pimephales promelas
PROVIDER: GSE15924 | GEO | 2009/05/13
SECONDARY ACCESSION(S): PRJNA116933
REPOSITORIES: GEO
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