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.
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