CAREER: Brain Aromatase Cytochrome P-450 and CNS Development

Lephart，Edwin D. 性类固醇激素可以通过某些酶从一类转化为另一类。 雄激素（例如睾酮）通过称为芳香化酶细胞色素P450的酶转化为雌激素在影响中枢神经系统的发育中起重要作用。 雌激素通过芳香化酶形成的巨大影响是造成男性和女性特定大脑区域结构差异的原因。 这些结构上的差异决定了中枢神经系统将如何按照沿着男性与女性的激素分泌模式和性行为的调节模式发挥作用。 这项研究将确定脑雌激素的生物合成是如何由芳香化酶基因控制的。 这将通过利用各种分子生物学技术来实现。 这些研究的目的是通过确定芳香化酶基因如何被激活的调控元件来确定脑芳香化酶调控的分子基础。 为了实现这一目标，Lephart博士将表征芳香酶基因转录起始位点上游的调控序列，以及这些元件在发育过程中是否发生变化。 研究雄激素对芳香化酶基因表达的调控，并研究大脑中编码这一关键酶的信息。 这些研究的结果将有助于了解大脑中的蛋白质如何控制对大脑基本中心发育至关重要的酶的表达。

IBN-9507972 Lephart, Edwin D. The sex steroid hormones can be transformed from one class to another by certain enzymes. The conversion of androgens (e.g. testosterone) to estrogens by an enzyme known as aromatase cytochrome P450 plays an important role in influencing the development of the central nervous system. The dramatic impact of estrogen formation via the aromatase enzyme is responsible for structural differences between males and females in specific brain regions. These structural differences determine how the central nervous system will function along male versus female patterns for hormone secretion and the regulation of sexual behavior. This study will determine how brain estrogen biosynthesis is controlled by the aromatase gene. This will be accomplished by utilizing various molecular biological techniques. The goal of these studies is to determine the molecular basis of brain aromatase regulation by determining the regulatory elements governing how the aromatase gene is activated. To accomplish this goal, Dr. Lephart will characterize the regulatory sequences upstream of the start site of transcription for the aromatase gene and whether these elements change during development. The regulation of aromatase gene expression by androgen will be investigated and the message in brain encoding this critical enzyme will also be studied. The outcome of these studies will allow the development of a picture about how the proteins in the brain control the expression of enyzmes critical for the development of essential centers in the brain.