脑芳香化酶细胞色素P450研究进展。

E D Lephart
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引用次数: 0

摘要

芳香化酶细胞色素P45 (P450AROM)酶活性在大脑特定区域催化雄激素向雌激素的转化。在中枢神经系统发育过程中,局部雌激素的形成影响神经结构的性别分化(即通过增加神经突生长和建立神经回路),并调节神经内分泌/生殖功能和性行为。早在20多年前的1970年,Naftolin等人就提供了雄激素被中枢神经内分泌组织芳构化的初步直接证据。这项工作为大脑芳香化酶假说奠定了基础。回顾过去和最近的数据揭示了脑芳香化酶在中枢神经系统的发育和功能中的重要性。本文根据最新的研究数据对芳香化酶假说进行了重新研究,并就芳香化酶的作用机制提出了新的理论建议。本文还介绍了芳香化酶细胞色素P450途径的雄激素代谢途径、脑芳香化酶的细胞类型、分布、发育特征和调控。最近的分子生物学研究检测了芳香化酶细胞色素P450在产前/产后发育过程中的表达,证明了脑芳香化酶的复杂性。来自这些研究的数据提供了对脑芳香化酶细胞色素P450基因调控的见解,并提出了脑芳香化酶表达的额外控制水平。这些发现为人类和啮齿类动物利用替代启动子驱动脑中芳香酶基因表达提供了证据。很明显,分子机制解释了芳香化酶在不同神经组织部位和不同生理状态或发育时期的不同表达。因此,芳香化酶细胞色素P450基因在产前和产后发育过程中调控局部雌激素生物合成的意义尚需进一步研究,因为这些雌激素分子对神经发育具有重大影响,并对生殖功能和行为产生影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A review of brain aromatase cytochrome P450.

Aromatase cytochrome P45 (P450AROM) enzyme activity catalyzes the conversion of androgens to estrogens in specific brains areas. During central nervous system development local estrogen formation influences the sexual differentiation of neural structures (i.e., by increasing neurite growth and establishing neural circuitry) and modulates neuroendocrine/reproductive functions and sexual behavior. More than 20 years ago, in 1970, Naftolin et al. provided preliminary direct evidence for the aromatization of androgens by central neuroendocrine tissues. This work created the foundation for the brain aromatase hypothesis. A review of past and recent data reveals the importance of brain aromatase in the development and function of the central nervous system. This review re-examines the aromatase hypothesis in light of recent data and a theoretical proposal is presented in reference to the aromatase mechanism. The metabolic pathway of androgen metabolism by the aromatase cytochrome P450 pathway, cell type, distribution, developmental profile, and regulation of brain aromatase is also presented. The complex nature of brain aromatase is exemplified by recent molecular biology studies examining the expression of aromatase cytochrome P450 during prenatal/postnatal development. Data derived from these studies provide insight into the regulation of the brain aromatase cytochrome P450 gene and suggest an additional level of control for the expression of brain aromatase. These findings present evidence for the utilization of alternative promoter(s) in man and rodents in driving aromatase gene expression in brain. It is clear that molecular mechanism(s) account for the diverse expression of aromatase in different neural tissue sites and during various physiological states or developmental periods. Therefore, further study is necessary in order to understand the significance of the regulation of local estrogen biosynthesis by the aromatase cytochrome P450 gene during prenatal and postnatal development due to the dramatic impact these estrogen molecules have on neural development and their influence on reproductive function and behavior.

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