Aromatization in Brain and Pituitary

大脑和垂体中的芳香化

• 批准号: 9605053
• 负责人: Gloria Callard
• 金额: $ 9.72万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 1999-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9605053&HistoricalAwards=false
• 关键词: Aromatization; Brain; Pituitary

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.

小行星9605053 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、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称为芳构化的过程从循环的性腺雄激素合成的。 雌激素的产生是由一种称为芳香酶的酶催化剂控制的，芳香酶是CYP 19基因的产物。 Callard博士有兴趣了解大脑如何产生雌激素和随后的雌激素依赖性神经过程的控制。 为了实现这一目标，她已经确定了一个模型系统，其中芳香酶和雄激素受体在大脑中非常高。 在研究该模型中对CYP 19基因表达起作用的分子机制时，Callard博士最近首次发现存在两个功能性CYP 19基因。 一种仅在脑和其他神经组织中高水平表达，第二种在脑和卵巢中表达水平低得多。 利用创新的分子技术，她现在将描述两个CYP19基因中每一个独特的分子机制。 由于脑形成的雌激素在胎儿和新生儿阶段的神经发育中起着至关重要的作用，并且在整个生命过程中参与了大脑功能的维持，因此Callard博士将利用这些信息来研究雌激素的产生是否针对不同细胞类型和神经回路中的时间，位置以及年龄，性别和激素状态等功能状况进行了优化。 这一新知识不仅将增加我们对雌激素在脑细胞内起作用的基本机制的理解，而且还将这一过程置于功能和进化的角度。