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 nuc leus may have a large impact upon its overall function. Hence, the ana tomical 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-bo th ovariectomized and not-were treated with a number of xenobiotic com pounds 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 react ion. Results of this investigation indicate the presence of mRNA for r eductase and P4502D isoforms throughout the rat brain. In addition, qu antitative PCR was utilized to demonstrate the effects of xenobiotics (phenobarbital, beta-naphthoflavone, imipramine) and sex hormones (tes tosterone, estrogen) on the levels of these messages in the female rat brain. Significant induction of message for P4502D forms was noted wi th testosterone in the absence of estrogen. The level of mRNA for redu ctase was not significantly influenced by any of the treatments, howev er. These results raise the issue of a sexual dimorphism in the rat re garding P4502D expression in brain.