Aromatization in Brain and Pituitary: Regulation of Reproduction in Vertebrates

来自性腺分泌物的循环雄激素转化为 雌二醇（神经雌激素）在大脑和垂体内。 这 转化，这是由一种酶复合物催化，称为 芳香化酶（P450arom）是雄激素充分表达所必需的 对脑性别分化、性行为和生殖的作用 神经内分泌学 因为大脑和垂体在结构上 功能复杂，神经雌激素的数量非常 小，很难确定P450 arom是如何调节的， 它精确的细胞和亚细胞定位， 以及神经雌激素发挥作用的机制。 卡勒德医生 已经确定了一种动物模型，金鱼，其中P450arom 活性比传统实验室高100到100倍 物种 此外，大脑雄激素受体也相应地 升高。 基于这种相关性和实验结果， 在最后一个项目期间，她假设了一种功能性的相互关系， P450arom和雄激素受体之间的关系， 雌激素作为一种正反馈调节剂， 用于阐明神经雌激素的类激素作用的终点 大脑和垂体。 为此，她建议隔离和 金鱼P450arom和雄激素cDNA探针的鉴定 受体基因，开发抗体来测量它们的蛋白质 产品，并将这些新工具应用于未回答的问题， 金鱼模型

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.