Bergh A F, Strobel H W
Department of Biochemistry and Molecular Biology, University of Texas Medical School at Houston 77030, USA.
Mol Cell Biochem. 1996 Sep 6;162(1):31-41. doi: 10.1007/BF00250993.
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.
由于大脑并非一个均质的器官，而是一个依赖众多部分精心协调相互作用的器官，一个核团中的病理变化可能会对其整体功能产生重大影响。因此，细胞色素P450单加氧酶系统在大脑中的解剖分布及其表达调控，对于阐明其在该器官中的功能至关重要。为了研究这些问题，对雌性大鼠（包括去卵巢和未去卵巢的）给予多种外源性化合物和性类固醇进行处理。将这些动物的大脑解剖成8个离散区域，并用聚合酶链反应测定细胞色素P4502D和细胞色素P450还原酶的信使核糖核酸的存在情况及相对水平。这项研究结果表明，在整个大鼠大脑中都存在还原酶和细胞色素P4502D同工型的信使核糖核酸。此外，利用定量聚合酶链反应来证明外源性化合物（苯巴比妥、β-萘黄酮、丙咪嗪）和性激素（睾酮、雌激素）对雌性大鼠大脑中这些信使核糖核酸水平的影响。在没有雌激素的情况下，睾酮可显著诱导细胞色素P4502D形式的信使核糖核酸。然而，还原酶的信使核糖核酸水平不受任何一种处理的显著影响。这些结果提出了大鼠大脑中细胞色素P4502D表达存在性二态性的问题。
