REGULATION OF HUMAN ESTROGEN SYNTHETASE

人类雌激素合成酶的调节

基本信息

项目摘要

Investigation into the regulation of estrogen biosynthesis in the human is one of the virtually unexplores frontiers of steroid hormone biochemistry that has important ramifications into such diverse areas as reproduction, sexual development and cancer. The experiments proposed in this study are designed to investigate mechanisms by which the activity and biosynthesis of estrogen synthetase (aromatase), the enzyme which converts androgens to estrogens, are regulated by natural processes in steroidogenic tissue. Aromatase from the microsomal fraction of human term placental tissue, a rich and easily available source of the human enzyme, will be purified and the components of the cytochrome P-450 mono-oxygenase system responsible for aromatization will be identified and characterized. The re-constitution of aromatase activity from its purified components will be studied as well as the effects of environment (e.g., pH, ionic strength, temperature, lipid composition), steroid (e.g., progestins, corticoids, androgens, estrogens) and non-steroid compounds (e.g., gonadotropins, protaglandins, cyclic AMP) on reconstituted aromatase and on placental microsomal aromatase. The rate-limitine component of aromatase in placental microsomes, trophoblast cell culture derived from human choriocarcinoma, and human ovarian tissued homogenate will be determined by incorporating each purified aromatase component individually into the membrane fraction of the system of interest and measuring the effect on the aromatization rate. Antibody to the purified aromatase components will be obtained and used, in conjunction with pulse-labeling with radioactive amino acids, to measure the rate of biosynthesis of these components in steroidogenic tissue (primary placental cell/organ culture, choriocarcinoma cell culture, primary ovarian granulosa cell culture) before and after stimulation of estrogen secretion by gonadotropins, prostaglandins and cyclic AMP.
对人体雌激素生物合成调节的研究是 类固醇激素生物化学中一个几乎未被探索的前沿领域, 这对生殖等不同领域产生了重要影响, 性发育和癌症 本研究中提出的实验是 旨在研究生物活性和生物合成的机制 雌激素合成酶(芳香酶),这种酶将雄激素转化为 雌激素受类固醇生成组织中的自然过程调节。 人足月胎盘组织微粒体芳香化酶 丰富和容易获得的人类酶的来源,将被纯化, 细胞色素P-450单加氧酶系统的组成部分 芳构化将被识别和表征。 的 从其纯化组分中重建芳香酶活性将是 研究以及环境的影响(例如,pH值,离子强度, 温度,脂质组成),类固醇(例如,孕激素,皮质激素, 雄激素、雌激素)和非甾体化合物(例如,促性腺激素, 前列腺素,环AMP)对重组芳香化酶和胎盘 微粒体芳香化酶 芳香化酶的限速成分 胎盘微粒体,人源性滋养层细胞培养物 绒毛膜癌和人卵巢组织匀浆将通过 将每种纯化的芳香酶组分单独地掺入到所述组合物中。 感兴趣系统的膜分数并测量对膜的影响 芳构化率 纯化的芳香酶组分的抗体将被纯化。 与放射性脉冲标记结合使用, 氨基酸,以测量这些组分的生物合成速率, 类固醇生成组织(原代胎盘细胞/器官培养,绒毛膜癌 细胞培养,原代卵巢颗粒细胞培养)前后 通过促性腺激素、前列腺素和前列腺素刺激雌激素分泌 环腺苷酸。

项目成果

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FRANCIS L BELLINO其他文献

FRANCIS L BELLINO的其他文献

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{{ truncateString('FRANCIS L BELLINO', 18)}}的其他基金

REGULATION OF HUMAN ESTROGEN SYNTHETASE
人类雌激素合成酶的调节
  • 批准号:
    3313777
  • 财政年份:
    1981
  • 资助金额:
    $ 2.35万
  • 项目类别:
REGULATION OF HUMAN ESTROGEN SYNTHETASE
人类雌激素合成酶的调节
  • 批准号:
    3313773
  • 财政年份:
    1981
  • 资助金额:
    $ 2.35万
  • 项目类别:
REGULATION OF HUMAN ESTROGEN SYNTHETASE
人类雌激素合成酶的调节
  • 批准号:
    3313776
  • 财政年份:
    1981
  • 资助金额:
    $ 2.35万
  • 项目类别:
REGULATION OF HUMAN ESTROGEN SYNTHETASE
人类雌激素合成酶的调节
  • 批准号:
    3313779
  • 财政年份:
    1981
  • 资助金额:
    $ 2.35万
  • 项目类别:
REGULATION OF HUMAN ESTROGEN SYNTHETASE
人类雌激素合成酶的调节
  • 批准号:
    3313778
  • 财政年份:
    1981
  • 资助金额:
    $ 2.35万
  • 项目类别:

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