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ToxSci Advance Access originally published online on March 21, 2006
Toxicological Sciences 2006 93(1):41-49; doi:10.1093/toxsci/kfj166
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

HIGHLIGHTED ARTICLE

Salicylate Disrupts Interrenal Steroidogenesis and Brain Glucocorticoid Receptor Expression in Rainbow Trout

Amélie Gravel and Mathilakath M. Vijayan1

Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada

Received January 26, 2006; accepted March 2, 2006

Varying levels of pharmaceuticals, including salicylate, ibuprofen, and acetaminophen, have been reported in the aquatic environment, but few studies have actually addressed the impact of these drugs on aquatic organisms. We tested the hypothesis that these pharmaceuticals are endocrine disruptors in fish by examining their impact on interrenal corticosteroidogenesis in rainbow trout. Indeed, acute adrenocorticotrophic hormone (ACTH)–mediated cortisol production in trout interrenal cells in vitro was significantly depressed (20–40%) by these pharmaceutical drugs. Furthermore, we investigated whether this interrenal dysfunction involved inhibition of the steroidogenic capacity in rainbow trout. To this end, we fed trout salicylate-laced feed (100 mg/kg body weight) for 3 days and assessed the transcript levels of key proteins involved in corticosteroidogenesis, including steroidogenic acute regulatory protein (StAR), peripheral-type benzodiazepine receptor (PBR), cytochrome P450 cholesterol side chain cleavage (P450scc), and 11ß-hydroxylase. Salicylate treatment did not affect the resting plasma cortisol or glucose levels, whereas the acute ACTH-stimulated cortisol production was significantly depressed in the interrenal tissue. This disruption of steroidogenesis by salicylate corresponded to a significant drop in the gene expression of StAR and PBR, but not P450scc or 11ß-hydroxylase, compared to the sham-treated fish. Also, brain glucocorticoid receptor (GR) protein content and not GR mRNA level was significantly reduced by salicylate. Taken together, salicylate is a corticosteroid disruptor in trout and the targets include the key rate-limiting step in interrenal steroidogenesis and brain glucocorticoid signaling.

Key Words: fish; Oncorhynchus mykiss; cortisol; StAR; peripheral-type benzodiazepine receptor; glucocorticoid receptor; ibuprofen; acetaminophen; NSAIDs.


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A. Hontela
Corticosteroidogenesis and StAR Protein of Rainbow Trout Disrupted by Human-Use Pharmaceuticals: Data for Use in Risk Assessment
Toxicol. Sci., September 1, 2006; 93(1): 1 - 2.
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