Aromatization in Brain and Pituitary

9605053雄鸭虽然雌激素通常被认为是一种来自卵巢、睾丸和胎盘的循环类固醇激素，但众所周知，这种激素也在大脑、脑下垂体和视网膜中产生。事实上，雌激素是在这些神经组织中通过一种被称为芳构化的过程从循环性腺雄激素中合成的。雌激素的产生是由一种名为芳香酶的酶催化剂控制的，芳香酶是CYP19基因的产物。卡拉德博士感兴趣的是了解大脑如何控制雌激素的产生以及随之而来的雌激素依赖神经过程。为了达到这个目标，她已经确定了一个模型系统，在这个模型系统中，芳香酶和雄激素受体在大脑中非常高。在研究该模型中影响细胞色素P19基因表达的分子机制时，Callard博士最近首次发现存在两个功能正常的细胞色素P19基因。一种只在大脑和其他神经组织中高水平表达，第二种在大脑和卵巢中表达水平要低得多。利用创新的分子技术，她现在将描述两个CYP19基因各自独特的分子机制。由于大脑形成的雌激素在胎儿和新生儿阶段的神经发育中起着关键作用，并与终生维持大脑功能有关，因此卡拉德博士将利用这些信息来研究谁的雌激素产生在不同细胞类型和神经回路中的时机、位置以及年龄、性别和荷尔蒙状态等功能状况方面是最佳的。这一新知识不仅将增加我们对雌激素在脑细胞内发挥作用的基本机制的理解，还将把这一过程置于功能和进化的角度。

9605053 Callard While estrogen is generally regarded as a circulating steroid hormone derived from ovaries, testes, and placenta, it is well-established that this hormone is also produced in the brain, pituitary, and retina. Indeed estrogen is synthesized in these neural tissues from circulating gonadal androgen through a process referred to as aromatization. Estrogen production is controlled by an enzyme catalyst termed aromatase, which is the product of the CYP19 gene. Dr. Callard is interested in understanding how brain production of estrogen and consequent estrogen-dependent neural processes are controlled. Towards this aim, she has identified a model system in which aromatase and androgen receptors are extremely high in the brain. In examining the molecular mechanisms operating on CYP19 gene expression in this model, Dr. Callard recently found, for the first time, the presence of two functional CYP19 genes. One is expressed at high levels in brain and other neural tissues exclusively, and the second is expressed at much lower levels in both brain and ovary. Using innovative molecular technology, she will now characterize the molecular mechanisms unique to each of the two CYP19 genes. Since brain-formed estrogens have a critical role in neural development during fetal and newborn stages and have been implicated in the maintenance of brain function throughout life, Dr. Callard will use this information to examine who estrogen production is optimized for timing, location in different cell-types and neural circuits, and functional condition such as age, gender and hormonal status. This new knowledge will not only increase our understanding of the basic mechanism by which estrogen becomes available to act within brain cells but also places this process into a functional and evolutionary perspective.