HORMONAL REGULATION OF AROMATASE IN ENDOMETRIUM

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个方面的研究：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。

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.