| Abstract: | Methoxychlor (MXC) has been shown to possess estrogenic activity in mammals and fish. Although MXC does not appear to appreciably bind the mammalian estrogen receptor, its demethylated metabolites have been shown to be significantly more potent agonists and are believed responsible for estrogenic effects in mammals following exposure to this pesticide. To determine whether catfish were capable of MXC demethylotion, and, hence, activation to a more estrogenic compound, in vitro biotransformation studies were carried out using hepatic microsomes from mature male channel catfish. Hepatic microsomes catalyzed the NADPH-dependent formation of monodemethylated (mono-MXC) and bisdemethylated (bis-MXC) metabolites of MXC. Treatment with mono-MXC at 40% of the MXC dose in catfish significantly induced serum vitellogenin (Vg) levels compared to MXC. Estrogen receptor binding studies in catfish liver cytosol showed that a racemic mixture of the mono-MXC had approximately 43 times the affinity for the receptor than MXC, but was still over 1000-fold less potent that 17β-estradiol. These results demonstrate that catfish are capable of biochemically activating MXC to a more potent hepatic estrogen receptor agonist. |
