Anatomical distribution of NADPH-cytochrome P450 reductase and cytochrome P4502D forms in rat brain: effects of xenobiotics and sex steroids.
Since the brain is not a homogeneous organ, but one dependent upon the well orchestrated interaction of numerous parts, pathology in one nucleus may have a large impact upon its overall function. Hence, the anatomical distribution of the P450 monoxygenase system in brain, as well as the regulation of its expression, is important in elucidating its function in that organ. In order to study these issues, female rats-both ovariectomized and not-were treated with a number of xenobiotic compounds and sex steroids. The brains from these animals were dissected into 8 discrete regions and the presence and relative level of message for P4502D and P450 reductase determined using polymerase chain reaction. Results of this investigation indicate the presence of mRNA for reductase and P4502D isoforms throughout the rat brain. In addition, quantitative PCR was utilized to demonstrate the effects of xenobiotics (phenobarbital, beta-naphthoflavone, imipramine) and sex hormones (testosterone, estrogen) on the levels of these messages in the female rat brain. Significant induction of message for P4502D forms was noted with testosterone in the absence of estrogen. The level of mRNA for reductase was not significantly influenced by any of the treatments, however. These results raise the issue of a sexual dimorphism in the rat regarding P4502D expression in brain.
Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston 77030, USA.
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D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007099:Imipramine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase; D010634:Phenobarbital / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology*; D015262:Xenobiotics / Q000494:pharmacology*; D019324:beta-Naphthoflavone / Q000494:pharmacology
D018076:DNA, Complementary; D004967:Estrogens; D012333:RNA, Messenger; D015262:Xenobiotics; D013739:Testosterone; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D007099:Imipramine; D010634:Phenobarbital