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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD019247-01A1
Application #
3316465
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1985-09-30
Project End
1986-08-31
Budget Start
1985-09-30
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Zhang, Wei; Mazella, James; Kloosterboer, Helenius J et al. (2006) Progestagenic effects of tibolone are target gene-specific in human endometrial cells. J Soc Gynecol Investig 13:459-65
Tang, Meiyi; Mazella, James; Zhu, Hui Hui et al. (2005) Ligand activated relaxin receptor increases the transcription of IGFBP-1 and prolactin in human decidual and endometrial stromal cells. Mol Hum Reprod 11:237-43
Mazella, J; Tang, M; Tseng, L (2004) Disparate effects of relaxin and TGFbeta1: relaxin increases, but TGFbeta1 inhibits, the relaxin receptor and the production of IGFBP-1 in human endometrial stromal/decidual cells. Hum Reprod 19:1513-8
Tseng, Linda; Tang, Meiyi; Wang, Zuncai et al. (2003) Progesterone receptor (hPR) upregulates the fibronectin promoter activity in human decidual fibroblasts. DNA Cell Biol 22:633-40
Tang, Meiyi; Mazella, James; Gao, Jiaguo et al. (2002) Progesterone receptor activates its promoter activity in human endometrial stromal cells. Mol Cell Endocrinol 192:45-53
Palejwala, Smita; Tseng, Linda; Wojtczuk, Andrea et al. (2002) Relaxin gene and protein expression and its regulation of procollagenase and vascular endothelial growth factor in human endometrial cells. Biol Reprod 66:1743-8
Gao, J; Mazella, J; Seppala, M et al. (2001) Ligand activated hPR modulates the glycodelin promoter activity through the Sp1 sites in human endometrial adenocarcinoma cells. Mol Cell Endocrinol 176:97-102
Gao, J; Mazella, J; Tang, M et al. (2000) Ligand-activated progesterone receptor isoform hPR-A is a stronger transactivator than hPR-B for the expression of IGFBP-1 (insulin-like growth factor binding protein-1) in human endometrial stromal cells. Mol Endocrinol 14:1954-61
Tseng, L; Mazella, J; Goligorsky, M S et al. (2000) Dopamine and morphine stimulate nitric oxide release in human endometrial glandular epithelial cells. J Soc Gynecol Investig 7:343-7
Tseng, L; Mazella, J (1999) Prolactin and its receptor in human endometrium. Semin Reprod Endocrinol 17:23-7

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