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ToxSci Advance Access published online on March 21, 2006
Toxicological Sciences, 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
Received January 26, 2006
Accepted March 2, 2006

Endocrine Toxicology

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

Amélie Gravel 1 and Mathilakath M. Vijayan 1 *

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

* To whom correspondence should be addressed.
Mathilakath M. Vijayan, E-mail: mvijayan{at}uwaterloo.ca


  Abstract

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 salicylatelaced feed (100 mg/kg body wt) for three days and assessed the transcript levels of key proteins involved in corticosteroidogenesis, including steroidogenic acute regulatory protein (StAR), peripherial-type benzodiazepine receptor (PBR), cytochrome P450 cholesterol side chain cleavage (P450scc) and 11{beta}-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 with a significant drop in the gene expression of StAR and PBR, but not P450scc or 11{beta}-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 ratelimiting step in interrenal steroidogenesis and brain glucocorticoid signaling.

Keywords: Fish; Oncorhynchus mykiss; cortisol; StAR; peripheral-type benzodiazepine receptor; glucocorticoid receptor; ibuprofen; acetaminophen; NSAIDs.
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