SYNTHESIS AND PURIFICATION OF BIOLOGICALLY IMPORTANT STEROID ANALOGS

该项目涉及碘化衍生物的制备和 雄激素和糖皮质激素家族中的类固醇激素类似物。 将开发允许合并的合成程序 将放射性碘(125I和123I)转化为具有以下两种元素之一的化合物 雄激素或糖皮质激素活性。被标记的雄激素有望 对雄激素反应性肿瘤的敏感检测有用，例如 用于前列腺癌和雄激素受体的体外定量。这个 放射性碘标记的雄激素也将对 放射自显影对组织的放射自显影研究，如大脑，其中雄激素 受体存在，但定位于特定的细胞或区域。是这样的 研究对于阐明雄激素在体内的作用具有很大的潜在价值。 胎儿大脑的性别分化等过程 发展。具有糖皮质激素活性的标记化合物将是 糖皮质激素受体富集区的定位和成像价值 大脑也是如此。因为特定的神经生理学机制 皮质类固醇对神经功能的影响尚不完全清楚，如 研究对于定义和理解这一角色越来越重要。 以及这些化合物在大脑中的功能。 在这项研究中，将制定出综合方法论 非放射性的碘化类固醇，将被提纯并完全 用标准的分析技术来表征。非放射性的 化合物将在竞争分析中进行受体结合测试。 被发现是有效竞争对手的化合物将与 放射性标记并更充分地测试结合亲和力(Ka或Kd)， 特异性和与类固醇血浆结合蛋白的结合。最终， 它们的激素或抗激素活性，受体介导的分布 体内，核转位和新陈代谢也将被确定。

This project is concerned with the preparation of iodinated derivatives and analogs of steroid hormones in the androgen and glucocorticoid families. Synthetic procedures will be developed which will permit the incorporation of radioactive iodine (125I and 123I) into compounds which have either androgenic or glucocorticoid activity. Labeled androgens are expected to be useful for the sensitive detection of androgen responsive tumors such as prostate cancer and for quantifying the androgen receptor in vitro. The radioiodinated androgens will also have great utility for the autoradiographic studies of tissues, such as brain, in which the androgen receptor is present, but localized in specific cells or regions. Such studies have great potential value in elucidating the role of androgens in processes such as the sexual differentiation of the brain in fetal development. Labeled compounds with glucocorticoid activity will be valuable in mapping and imaging of glucocorticoid receptor rich regions of the brain also. Since the specific neurophysiological mechanisms by which corticosteroids influence neuronal function are not fully understood, such studies are of increasing importance in defining and understanding the role and function of these compounds in the brain. In this study the synthetic methodology will be worked out for the nonradioactive iodinated steroids, which will be purified and fully characterized using standard analytical techniques. The nonradioactive compounds will be tested for receptor binding in competition assays. Compounds found to be effective competitors will be prepared with the radioactive label and tested more fully for binding affinity (ka or Kd), specificity and binding to steroid plasma binding proteins. Eventually, their hormonal or antihormonal activity, receptor mediated distribution in vivo, nuclear translocation and metabolism will also be determined.