Modulation of brain steroidogenesis by affecting transcriptional changes of steroidogenic acute regulatory (StAR) protein and cholesterol side chain cleavage (P450scc) in juvenile Atlantic salmon (Salmo salar) is a novel aspect of nonylphenol toxicity.
Gene expression patterns for key brain steroidogenic (StAR, P450scc, CYP11beta) and xenobiotic- and steroid-metabolizing enzymes (CYP1A1 and CYP3A) have been investigated in waterborne nonylphenol (5, 15, and 50 microg/ L) treated juvenile Atlantic salmon (Salmo salar), in addition to carrier vehicle (ethanol) exposed fish, sampled at different time intervals (0, 3, and 7 days) after exposure. Gene expression patterns were studied using the quantitative polymerase chain reaction (real-time PCR). Treatment of juvenile salmon with nonylphenol caused significant induction of steroidogenic acute regulatory (StAR) protein mRNA at day 7 postexposure in the group receiving 15 microg of nonylphenol/L. P450scc was first induced in the group treated with 5 microg of nonylphenol/L at day 7; thereafter, an apparent nonylphenol-concentration-dependent decrease in P450scc mRNA was observed. CYP11beta mRNA was significantly induced at day 3 after exposure to 5 betag of nonylphenol/L; thereafter, CYP11beta mRNA levels were inhibited below control levels in the 15 and 50 microg of nonylphenol/L groups at day 3. At day 7, significant induction of CYP11beta mRNA was observed only in the group exposed to 15 microg of nonylphenol/L. For CYP1A1 mRNA, apparent nonylphenol-concentration-dependent decreases were observed at day 7 postexposure. CYP3A mRNA was significantly induced by all nonylphenol exposure concentrations at day 7. When exposed groups were compared, CYP3A transcript was significantly induced between 5 and 15 microg of nonylphenol/ L, and decreased between 15 and 50 microg of nonylphenol/ L. The ethanol control showed a significant reduction of CYP3A mRNA at day 3 postexposure. The present study has demonstrated variations in three key steroidogenic proteins and xenobiotic- and steroid-metabolizing CYP isoenzyme gene transcripts in the brain of nonylphenol-exposed juvenile salmon. Therefore, the present study represents a novel aspect of neuroendocrine effects of nonylphenol in fish not previously demonstrated and should be studied in more detail.
Department of Biology, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, 7491 Trondheim, Norway. arukwe@bio.ntnu.no
Augustine
A
Arukwe
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000187:drug effects* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020317:Salmo salar; D014158:Transcription, Genetic / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000098682:Steroidogenic Acute Regulatory Protein
D010636:Phenols; D010750:Phosphoproteins; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; D000098682:Steroidogenic Acute Regulatory Protein; C025256:nonylphenol; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D002786:Cholesterol Side-Chain Cleavage Enzyme