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Peroxisome proliferator-activated receptors, estrogenic responses and biotransformation system in the liver of salmon exposed to tributyltin and second messenger activator.

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Peroxisome proliferator-activated receptors, estrogenic responses and biotransformation system in the liver of salmon exposed to tributyltin and second messenger activator.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Pavlikova, Nela Kortner, Trond M. Arukwe, Augustine
Description	Country affiliation: Norway Author Affiliation: Pavlikova N ( Department of Biology, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, 7491 Trondheim, Norway.)
Abstract	The mechanisms by which organotin compounds produce modulations of the endocrine systems and other biological responses are not fully understood. In this study, juvenile salmon were force-fed diet containing TBT (0: solvent control, 0.1, 1 and 10mg/kg fish) for 72 h. Subsequently, fish exposed to solvent control and 10mg TBT were exposed to waterborne concentration (200 microg/l) of the adenylate cyclase (AC) stimulator, forskolin for 2 and 4h. The overall aim of the study was to explore whether TBT endocrine disruptive effects involve second messenger activation. Liver was sampled from individual fish (n=8) at the end of the exposures. The transcription patterns of peroxisome proliferator-activated receptor (PPAR) isotype and acyl-coenzyme A oxidase 1 (ACOX1), aromatase isoform, estrogen receptor-alpha (ER alpha), pregnane X receptor (PXR), CYP3A and glutathione S-transferase (GST) genes were measured by quantitative polymerase chain reaction (qPCR). Our data showed a consistent increase in PPAR alpha, PPAR beta and PPAR gamma mRNA and protein expression after TBT exposure that were inversely correlated with ACOX1 mRNA levels. Forskolin produced PPAR isotype-specific mRNA and protein effects that were modulated by TBT. ACOX1 expression was decreased (at 2h) and increased (at 4h) by forskolin and the presence of TBT potentiated these effects. TBT apparently increased mRNA and protein levels of cyp19a, compared to the solvent control, whereas cyp19b mRNA levels were unaffected by TBT treatment. Combined TBT and forskolin exposure produced respective decrease and increase of mRNA levels of cyp19a and cyp19b, compared with control. TBT decreased ER alpha mRNA at low dose (1mg/kg) and forskolin exposure alone produced a consistent decrease of ER alpha mRNA levels that were not affected by the presence of TBT. Interestingly, PXR and CYP3A mRNA levels were differentially affected, either decreased or increased, after exposure to TBT and forskolin, singly and also in combination. GST mRNA was increased by TBT exposure. Exposure to forskolin alone increased GST expression with time, and combined exposure with TBT potentiated these respective effects. Overall, the present study demonstrates multiple biological effects of TBT given singly or in combination with cAMP activator. There are no studies known to us that have evaluated the endocrine disruptive effects of TBT in the presence of a second messenger activator, and our data suggest that TBT may exert endocrine, biotransformation and lipid peroxidative effects through modulation of cAMP/PKA second messenger signaling with overt physiological consequences.
File Format	HTM / HTML
ISSN	0166445X
Issue Number	2
Volume Number	99
e-ISSN	18791514
Journal	Aquatic Toxicology
Language	English
Publisher	Elsevier
Publisher Date	2010-08-15
Publisher Place	Netherlands
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Toxicology Environmental Exposure Gene Expression Regulation Drug Effects Liver Peroxisome Proliferator-activated Receptors Metabolism Salmo Salar Trialkyltin Compounds Toxicity Water Pollutants, Chemical Acyl-coa Oxidase Animals Aromatase Biotransformation Cytochrome P-450 Cyp3a Estrogen Receptor Alpha Enzymology Rna, Messenger Receptors, Steroid Second Messenger Systems Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Aquatic Science

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Modulation of acute steroidogenesis, peroxisome proliferator-activated receptors and CYP3A/PXR in salmon interrenal tissues by tributyltin and the second messenger activator, forskolin.

Effects of tributyltin (TBT) on in vitro hormonal and biotransformation responses in Atlantic salmon (Salmo salar).

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Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to alpha and gamma isoforms of peroxisome-proliferator-activated receptors by competing with agonists.

Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression.

Expression of peroxisome proliferator-activated receptors in zebrafish (Danio rerio) depending on gender and developmental stage

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The peroxisome proliferator (PP) response element upstream of the human acyl CoA oxidase gene is inactive among a sample human population: significance for species differences in response to PPs

Peroxisome proliferator-activated receptors, estrogenic responses and biotransformation system in the liver of salmon exposed to tributyltin and second messenger activator.

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Peroxisome proliferator-activated receptors, estrogenic responses and biotransformation system in the liver of salmon exposed to tributyltin and second messenger activator.