Progestins, progesterone receptor modulators, and progesterone antagonistschange VEGF release of endometrial cells in culture

The influences of the synthetic progestin, medroxyprogesterone acetate (MPA ), the progesterone receptor modulator J867, and the antagonist ZK137316 we re studied in vitro on isolated endometrial epithelial cells, as well as en dometrial fibroblasts. We evaluated the expression of estrogen receptor alp ha (ER) and the progesterone receptor (PR) by RT-PCR. ER and PR were strong ly expressed in the fibroblasts and epithelial cells under treatment with 1 0(-8) M 17 beta -estradiol (E-2). Treatment with 10(-6) M J867 or ZK137316 upregulated the PR expression as did E-2 in contrast to treatment with 10-6 M MPA, which caused a downregulation of PR in epithelial cells, but not in fibroblasts. In addition, the vascular endothelial growth factor (VEGF) re lease into the cell culture medium was analyzed by a VEGF-ELISA. VEGF which plays an important role in angiogenesis, is regulated by steroid hormones as well as hypoxia. E-2 stimulates VEGF release into the medium in both cel l types, MPA reduces VEGF release significantly in the fibroblast cell cult ure, but increases it in the epithelial cell culture. ZK137316. in the pres ence or absence of E-2, reduces VEGF release in fibroblast cell culture. J8 67 increases the VEGF production in fibroblasts only in the presence of E-2 . Both compounds show no significant effects, compared to E-2, in epithelia l cell culture. The different results for the epithelial cells and fibrobla sts indicate that the pharmacological effects of PR modulators (PRMs) and p rogesterone antagonists (PAs) may be cell specific and depend on the presen ce or absence of partial progestagenic agonistic activities. This observati on opens up new perspectives for various clinical applications. (C) 2000 El sevier Science Inc. All rights reserved.