Aromatization in Brain and Pituitary: Regulation of Reproduction in Vertebrates

大脑和垂体中的芳香化：脊椎动物繁殖的调节

• 批准号: 8916809
• 负责人: Gloria Callard
• 金额: $ 36.28万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8916809&HistoricalAwards=false
• 关键词: Aromatization; Brain; Pituitary; Regulation; Reproduction

Circulating androgen derived from gonadal secretions is converted to estradiol (neuroestrogen) within the brain and pituitary. This transformation, which is catalyzed by an enzyme complex termed aromatase (P450arom), is essential for the full expression of androgen actions on brain sex differentiation, sex behavior and reproductive neuroendocrinology. Because the brain and pituitary are structurally and functionally complex and the quantity of neuroestrogen is very small, it has been difficult to determine how P450arom is regulated, its precise cellular and subcellular location, and the cellular targets and mechanisms by which neuroestrogen exerts its actions. Dr. Callard has identified an animal model, the goldfish, in which P450arom activity is 100-to-100- times higher than in conventional laboratory species. Moreover, brain androgen receptors are correspondingly elevated. Based on this correlation and results of experiments during the last project period, she postulates a functional interrrelationship between P450arom and androgen receptors in which locally synthesized estrogen acts as a positive feedback regulator of quantifiable endpoints for elucidating the parahormonal role of neuroestrogen in brain and pituitary. To this end, she proposes to isolate and characterize cDNA probes for the goldfish P450arom and androgen receptor genes, to develop antibodies for measuring their protein products, and to apply these new tools to unanswered questions using the goldfish model.

来自性腺分泌物的循环雄激素在大脑和垂体内转化为雌二醇（神经雌激素）。这种转化是由一种称为芳香化酶（P450arom）的酶复合物催化的，对于雄激素在脑性别分化、性行为和生殖神经内分泌学中的充分表达至关重要。由于脑和垂体结构和功能复杂，而神经雌激素的数量非常少，因此很难确定P450arom是如何调节的，其精确的细胞和亚细胞位置，以及神经雌激素发挥作用的细胞靶点和机制。卡拉德博士已经确定了一种动物模型——金鱼，其P450arom的活性比传统实验室物种高100到100倍。此外，脑雄激素受体也相应升高。基于这一相关性和上一期项目期间的实验结果，她假设P450arom与雄激素受体之间存在功能上的相互关系，其中局部合成的雌激素作为可量化终点的正反馈调节器，以阐明神经雌激素在脑和垂体中的副激素作用。为此，她建议分离和表征金鱼P450arom和雄激素受体基因的cDNA探针，开发用于测量其蛋白质产物的抗体，并将这些新工具应用于金鱼模型中未解决的问题。