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

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 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 11beta-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 11beta-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.

Disruption of glucocorticoid action by environmental chemicals: Potential mechanisms and relevance

“…Treatment of rainbow trout with high doses of salicylate decreased interrenal cortisol production [42]. While resting plasma cortisol or glucose levels were not changed, the acute ACTH-stimulated cortisol production was significantly reduced.…”

Glucocorticoid receptor activation following elevated oocyte cortisol content is associated with zygote activation, early embryo cell division, and IGF system gene responses in rainbow trout

“…The primary GR antibody used was anti-trout GR IgG serum raised in rabbits (Sathiyaa & Vijayan 2003). This antibody has been proven to be an effective GR anti-serum in rainbow trout , Aluru et al 2004, Gravel & Vijayan 2006. The antibody was used at a 1:500 dilution in PBS.…”

Steroidogenic acute regulatory (StAR) protein and cholesterol side-chain cleavage (P450scc)-regulated steroidogenesis as an organ-specific molecular and cellular target for endocrine disrupting chemicals in fish

“…3. In another study by Gravel and Vijayan (2006), it was demonstrated that pharmaceutical endocrine disruptors impacted interrenal corticosteroidogenesis in rainbow trout through the alteration of acute adrenocorticotrophic hormone (ACTH)-mediated cortisol production in trout interrenal cells in vitro. These authors showed that the interrenal dysfunction involved inhibition of steroidogenic capacity, corresponding with decreased expression of the StAR and peripheral-type benzodiazepine receptor (PBR) mRNA, but not P450scc or 11β-hydroxylase (11β-OH).…”

“…These authors showed that the interrenal dysfunction involved inhibition of steroidogenic capacity, corresponding with decreased expression of the StAR and peripheral-type benzodiazepine receptor (PBR) mRNA, but not P450scc or 11β-hydroxylase (11β-OH). In addition, brain glucocorticoid receptor (GR) protein content, but not GR mRNA level, was significantly reduced by salicylate (Gravel and Vijayan 2006).…”