MECHANISM AND CONTROL OF ESTROGEN BIOSYNTHESIS

雄激素向雌激素的转化涉及三个羟基化， 其中前两个发生在C-19位置，第三个发生在2Beta位置。 这些反应的产物2 β-羟基-19-醛是 非酶转化为雌激素。 2 β-羟基的抗体 乙醛已经制备，它通过延迟雌激素的形成来抑制雌激素的形成。 胎盘芳香化酶的不稳定酶产物的崩溃。 的 本项目的目的是利用这种免疫探针和高 已合成的比活性雄激素底物， 检查参与雌激素的各个羟基化 在胎盘以外的组织中，如性腺、脑 和脂肪组织。 芳构化序列中的步骤为 将通过上述方法分析垂体激素的影响 probes. 新的放射性标记底物将用于检查 对比正常人的体内研究中外周芳构化的变化 和体重扭曲的受试者，以及肝脏疾病患者， 疾病 雌激素的生物合成机制将为雌激素的生物合成提供依据。 结构的综合，力求有效和具体 芳构化抑制剂，并且可以证明是有用的治疗剂， 需要停止雌激素生物合成的疾病。

The transformation of androgens to estrogens involves three hydroxylations, the first two of which take place at the C-19 position and third at 2Beta. The product of these reactions the 2Beta-hydroxy-19-aldehyde, is transformed nonenzymatically to estrogen. An antibody to the 2Beta-hydroxy aldehyde has been prepared and it inhibits estrogen formation by delaying the collapse of the labile enzymatic product of placental aromatase. The purpose of this project is to utilize this immunological probe and the high specific activity androgen substrates which have been synthesized, to examine the individual hydroxylations participating in estrogen biosynthesis in tissues other than the placenta such as the gonads, brain and adipose tissue. The step(s) in the aromatization sequence which are influenced by pituitary hormones will be analyzed by means of the above probes. The new radiolabeled substrates will be employed to examine changes in peripheral aromatization in in vivo studies contrasting normals and subjects with body weight distortions, as well as patients with liver disease. The mechanism of estrogen biosynthesis will provide the basis for the synthesis of structures which bid well to be effective and specific aromatization inhibitors and can prove to be useful therapeutic agents in diseases in which cessation of estrogen biosynthesis is desirable.