Rosenbrock H, Hagemeyer C E, Ditter M, Knoth R, Volk B
Neurocentre, Department of Neuropathology, University of Freiburg, Germany.
J Neurochem. 2001 Jan;76(2):332-40. doi: 10.1046/j.1471-4159.2001.00011.x.
Despite the very small amounts of cytochrome P450 (P450, CYP) enzymes expressed in different areas and cell populations of the brain as compared with the liver, there is significant evidence for their specific involvement in brain development, function and plasticity. Nevertheless, the current discussion about occurrence and importance of cerebral cytochrome P450s is determined by inconsistent interpretations of their function in general and with respect to single isoforms. Continuing a series of publications about brain P450 isoforms, we now present evidence for the constitutive expression of CYP2B1 and CYP2B2 mRNAs in rat brain. Immunocytochemical and non-radioactive in situ hybridization studies revealed the same expression pattern throughout the brain predominantly in neuronal populations, but to some extent in astrocytes of corpus callosum and olfactory bulb. The well known testosterone-metabolizing capacity and the presence of CYP2B isoforms shown in steroid hormone-sensitive areas and neurones (e.g. hippocampus) clarify the significance of isoforms like CYP2B1 and CYP2B2 for impairment of steroid hormone actions by P450 inducing environmental substances. We argue that cerebral P450 isoforms which are induced by xenobiotics and are able to metabolize these as well as endogenous substrates help us to understand fundamental aspects of brain's functioning.
与肝脏相比，尽管细胞色素P450（P450，CYP）酶在脑的不同区域和细胞群体中表达量极少，但有大量证据表明它们在脑发育、功能和可塑性方面发挥着特定作用。然而，目前关于脑细胞色素P450的存在及其重要性的讨论，是由对其总体功能以及单个亚型功能的不一致解读所决定的。在一系列关于脑P450亚型的出版物基础上，我们现在提供大鼠脑中CYP2B1和CYP2B2 mRNA组成性表达的证据。免疫细胞化学和非放射性原位杂交研究表明，在整个大脑中，相同的表达模式主要存在于神经元群体中，但在胼胝体和嗅球的星形胶质细胞中也有一定程度的表达。在类固醇激素敏感区域和神经元（如海马体）中显示出的众所周知的睾酮代谢能力以及CYP2B亚型的存在，阐明了CYP2B1和CYP2B2等亚型对于P450诱导性环境物质损害类固醇激素作用的重要性。我们认为，由外源性物质诱导并能够代谢这些物质以及内源性底物的脑细胞色素P450亚型，有助于我们理解脑功能的基本方面。
