Lephart E D
Department of Zoology, Brigham Young University, Provo, UT 84602, USA.
Brain Res Brain Res Rev. 1996 Jun;22(1):1-26.
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.
芳香化酶细胞色素P45（P450AROM）的酶活性在特定脑区催化雄激素转化为雌激素。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/生殖功能及性行为。20多年前，即1970年，纳夫托林等人提供了中枢神经内分泌组织将雄激素芳香化的初步直接证据。这项工作为脑芳香化酶假说奠定了基础。对过去和近期数据的回顾揭示了脑芳香化酶在中枢神经系统发育和功能中的重要性。本综述根据近期数据重新审视了芳香化酶假说，并就芳香化酶机制提出了一项理论建议。还介绍了芳香化酶细胞色素P450途径对雄激素代谢的代谢途径、细胞类型、分布、发育情况及脑芳香化酶的调节。近期分子生物学研究对产前/产后发育过程中芳香化酶细胞色素P450表达的研究，例证了脑芳香化酶的复杂性。这些研究得出的数据有助于深入了解脑芳香化酶细胞色素P450基因的调节，并提示了脑芳香化酶表达的另一控制水平。这些发现为人类和啮齿动物利用替代启动子驱动脑中芳香化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以及各种生理状态或发育时期的多样表达。因此，鉴于这些雌激素分子对神经发育有显著影响，并对生殖功能和行为有影响，有必要进一步研究以了解产前和产后发育过程中芳香化酶细胞色素P450基因对局部雌激素生物合成调节的意义。
