title: Aryl hydrocarbon receptor activation impairs cortisol response to stress in rainbow trout by disrupting the rate-limiting steps in steroidogenesis.
abstract: Anthropogenic stressors activating aryl hydrocarbon (Ah) receptor signaling, including polychlorinated biphenyls, impair the adaptive corticosteroid response to stress, but the mechanisms involved are far from clear. Using Ah receptor agonist (beta-naphthoflavone; BNF) and antagonist (resveratrol; RVT), we tested the hypothesis that steroidogenic pathway is a target for endocrine disruption by xenobiotics activating Ah receptor signaling. Trout (Oncorhynchus mykiss) were fed BNF (10 mg/kg.d), RVT (20 mg/kg.d) or a combination of both for 5 d, and subjected to a handling disturbance. BNF induced cytochrome P4501A1 expression in the interrenal tissue and liver, whereas this response was abolished by RVT, confirming Ah receptor activation. In control fish, handling disturbance transiently elevated plasma cortisol and glucose levels and transcript levels of interrenal steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage (P450scc) and 11beta-hydroxylase over a 24-h period. BNF treatment attenuated this stressor-induced plasma and interrenal responses; these BNF-mediated responses were reverted back to the control levels in the presence of RVT. We further examined whether these in vivo impacts of BNF on steroidogenesis can be mimicked in vitro using interrenal tissue preparations. BNF depressed ACTH-mediated cortisol production, and this decrease corresponded with lower StAR and P450scc, but not 11beta-hydroxylase mRNA abundance. RVT eliminated this BNF-mediated depression of interrenal corticosteroidogenesis in vitro. Altogether, xenobiotics activating Ah receptor signaling are steroidogenic disruptors, and the mode of action includes inhibition of StAR and P450scc, the rate-limiting steps in steroidogenesis.
authors.affiliation: Department of Biology, University of Waterloo, Ontario, Canada.
authors.forename: Neelakanteswar
authors.initials: N
authors.lastname: Aluru
authors.forename: Mathilakath M
authors.initials: MM
authors.lastname: Vijayan
mesh_terms: D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D006854:Hydrocortisone / Q000097:blood*; D017686:Oncorhynchus mykiss; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013315:Stress, Psychological / Q000378:metabolism*; D019324:beta-Naphthoflavone / Q000633:toxicity; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000305:Adrenal Cortex Hormones; D001786:Blood Glucose; D010750:Phosphoproteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D000098682:Steroidogenic Acute Regulatory Protein; D019324:beta-Naphthoflavone; D019363:Cytochrome P-450 CYP1A1; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006854:Hydrocortisone