MECHANISM AND CONTROL OF ESTROGEN BIOSYNTHESIS

雌激素生物合成的机制和控制

• 批准号: 3315387
• 负责人: JACK FISHMAN
• 金额: $ 12.5万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-02-01 至 1987-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3315387
• 关键词: N hydroxylation; brain metabolism; cyclization; estrogens; hormone biosynthesis; hormone regulation /control mechanism; human tissue; liver disorder; radiotracer; scintillation spectrometry; stereochemistry

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.

雄激素向雌激素的转化涉及三个羟化作用， 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2Beta-羟基-19-醛是 非酶转化为雌激素。抗2-β-羟基的抗体 已经制备了醛，它通过延缓雌激素的形成来抑制雌激素的形成 胎盘芳香酶不稳定的酶产物的崩溃。这个 本项目的目的是利用这一免疫探针和高效的 已合成的比活性雄激素底物，以 检查参与雌激素的个体羟化作用 胎盘以外的组织中的生物合成，如性腺、脑 和脂肪组织。芳构化序列中的步骤(S)是 对垂体激素的影响将通过上述手段进行分析。 探测器。新的放射性标记基板将被用于检查 与正常对照的活体研究中周围芳构化的变化 和体重扭曲的受试者，以及肝病患者 疾病。雌激素的生物合成机制将为 有效和特定的结构的合成 芳构化抑制剂，可以被证明是有用的治疗剂 需要停止雌激素生物合成的疾病。