title: Brain transcriptomics in response to beta-naphthoflavone treatment in rainbow trout: the role of aryl hydrocarbon receptor signaling.
abstract: Polychlorinated biphenyls (PCBs) exposure disrupts steroid production in teleostean fishes. While this suppression of plasma steroid levels is thought to involve aryl hydrocarbon receptor (AhR) signaling, the target tissues impacted and the molecular mechanisms involved have rarely been addressed. We tested the hypothesis that AhR activation downregulates genes involved in neuroendocrine function, including the control of brain-pituitary-interrenal (BPI) and -gonadal (BPG) axes in rainbow trout. To elucidate receptor-specific signaling, we utilized a pharmacological approach using beta-naphthoflavone (BNF) and resveratrol (RVT) as AhR agonist and antagonist, respectively. The gene expression pattern in the brain was analysed using a low-density targeted trout cDNA array enriched with genes encoding proteins involved in endocrine signaling, stress response and metabolic adjustments. Upregulation of AhR and CYP1A1 gene expression with BNF and the inhibition of this response by RVT confirmed AhR-dependent signaling. RVT by itself impacted only a few genes, while BNF treatment significantly modulated the transcript level of 49 genes, many of which are involved in the neuroendocrine control of stress and reproduction. Of these, only 27% of the BNF-mediated transcriptional response was blocked by RVT, suggesting molecular regulation of neuroendocrine pathways that are also AhR-independent. Gene expression pattern for select genes seen with the microarray analysis was also confirmed using quantitative real-time PCR. Overall, our results reveal for the first time that BNF disrupts several key genes involved in the neuroendocrine control of stress and sex steroid biosynthesis, while the mode of action involves both AhR-dependent and -independent pathways in trout.
authors.affiliation: Department of Biology, University of Waterloo, 200 University Avenue West, Ontario, Canada N2L 3G1.
authors.forename: Neelakanteswar
authors.initials: N
authors.lastname: Aluru
authors.forename: Mathilakath M
authors.initials: MM
authors.lastname: Vijayan
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000235:genetics / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017686:Oncorhynchus mykiss; D016133:Polymerase Chain Reaction / Q000379:methods; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology*; D013312:Stress, Physiological / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D012739:Gonadal Steroid Hormones; D018336:Receptors, Aryl Hydrocarbon; D013267:Stilbenes; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D000077185:Resveratrol