HORMONAL REGULATION OF AROMATAES IN ENDOMETRIUM

子宫内膜中芳香剂的激素调节

• 批准号: 3316467
• 负责人: LINDA TSENG
• 金额: $ 9.52万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3316467
• 关键词: cyclic AMP; cytochrome P450; endometrium; estrogens; gel filtration chromatography; hormone biosynthesis; hormone regulation /control mechanism; human tissue; progesterone; radiotracer; scintillation spectrometry; tissue /cell culture

Progesterone (P) stimulates the aromatase activity in human endometrial stromal cells and estrogen (E. estradiol and estrone) potentiates this stimulation. In contrast, P suppresses the aromatase activity in ovarian granulosa cells and in endometrial glandular epithelial cells. The objective of this proposal is to evaluate the effects of P and E on the intracellular biochemical changes that leads to the stimultion and supression of the aromatase activity. The research plans include the following studies: 1) the modulation of aromatase activity in endometrial stromal cells by varying the doses of P or P + E and incubation times; 2) the identification of intracellular mediators for the actions of P and E on aromatase system: PR, cAMP, or specific P and E binding proteins on cell membrane and in microsomes; 3) the effect of P and E on new proteins synthesis of the aromatase enzyme system: the rate of incorporation of radioactive amino acids into NADPH cytochrome c reductase and cytochrome P-450 specific to aromatase. The proposed study will be carried out in human endometrium, an organ which has no production of P and minimal production of E. Thus, any effect of P and E on aromatase system can be evaluated without the interference of endogenous P and E. This project will reveal the mechansim of the regulations of aromatase by P and E. It will demonstrate the synergistic and antagonistic effects of P and E on the regulation of the rate of estrogen synthesis and its actions on the target tissue and provide evidence for a new pathway of the action of steriod hormones, i.e. to link P and E to the cAMP system for the hormonal regulation of aromatase.

孕酮(P)刺激人子宫内膜芳香酶活性 基质细胞和雌激素(雌二醇和雌酮)会加强这一点。 刺激。相反，P抑制卵巢芳香酶活性 颗粒细胞和子宫内膜腺上皮细胞。 这项建议的目标是评估P和E对 细胞内生化变化导致刺激和 抑制芳香酶活性。 研究计划包括以下几方面的研究：1)调制 不同剂量P对子宫内膜间质细胞芳香化酶活性的影响 或P+E和孵育时间；2)细胞内鉴定 P和E对芳香酶系统作用的中介物：PR、cAMP或 细胞膜和微粒体上的P和E结合蛋白；3) P和E对芳香酶新蛋白合成的影响 系统：放射性氨基酸掺入NADPH的速率 芳香酶特有的细胞色素C还原酶和细胞色素P-450。 这项拟议的研究将在人类子宫内膜中进行，子宫内膜是一种 没有P的产生和E的最小产生，因此，P的任何影响 和E可在不受干扰的情况下进行测定。 内源P和E。 本课题将揭示P。芳香酶的调控机制。 和E.将展示P的协同和拮抗作用。 和E对雌激素合成速率的调节及其作用 并为新的作用途径提供证据 类固醇激素，即将P和E连接到cAMP系统 芳香酶的激素调节。