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.