Sammendrag
A great challenge in pharmacology and toxicology is to understand the molecular mechanisms behind how mixtures of compounds affect living organisms. During smoltification, Atlantic salmon parr undergo several hormonal and physiological changes and TH is known to play an integral role via hormone-bound nuclear receptors. CYP3A enzymes are responsible for the oxidative metabolism of a wide array of endobiotic and xenobiotic compounds. The present study was designed to investigate the ability of DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) to interact with the TH nuclear receptors, the PXR and CYP3A gene expression. Atlantic salmon parrs were exposed continuously to waterborne DDE (10 g/L) and thyroxine (T4; 50 g/l) singly and also in combination. Liver, brain and kidney samples were collected after 5 days and gene expression patterns for IGF-1R, TR, TR, TSH, PXR and CYP3A were analysed using quantitative RT-PCR with gene specific primers. Our data show that T4 and DDE caused significant induction of hepatic CYP3A gene expression, singly and in combination and this effect correlates with PXR transcript patterns. In the brain, T4 and DDE given singly caused significant elevation of TR gene expression, while combined exposure did not affect brain TR transcript levels. DDE when given singly and in combination with T4 caused significant induction of liver TR, while T4 did not cause changes in brain, kidney and liver TR mRNA levels. DDE exposure caused significant elevation of TSH mRNA levels in the liver, and inhibited the same response in the brain. Exposure to T4 singly and in combination with DDE inhibited TSH mRNA levels in brain. The present study documents for the first time in an anadromous fish species, the effects of DDE on CYP3A/PXR and TH-dependent gene expression patterns with possible physiological and hormonal consequences for salmon parr during smoltification.
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