EFFECTS OF STEROID-HORMONES ON FIBRINOLYTIC SYSTEM IN CULTURED HUMAN ENDOMETRIAL CELLS

In a primary human endometrial cell culture, the addition of progester one resulted in an approximately 2-fold increase in the amount of tiss ue-type plasminogen activator (t-PA) released into the culture media, with the minimal effective dose being 10(-7) M. In contrast, progester one significantly reduced the release of urokinase-type PA (u-PA). End ometrial cells are known to release a major PA inhibitor, PAI-1. Proge sterone stimulated the release of PAI-1. These observed effects of pro gesterone seem to be mediated through the progestin receptor in that R 5020, a specific ligand for progestin receptor, mimicked the effects o f progesterone, and RU486, an antagonist of progesterone, completely e liminated the effects of progesterone. It is notable that estradiol, w hen added alone or in combination with progesterone, caused no discern ible effect on the release of PAs and PAI-1. These results suggest tha t progesterone is a key hormone in regulating the PA/plasmin system in the human endometrum, thereby playing a pivotal role in implantation and ensuing embryonal development.