STEROID-MODULATED STROMAL CELL TISSUE FACTOR EXPRESSION - A MODEL FORTHE REGULATION OF ENDOMETRIAL HEMOSTASIS AND MENSTRUATION

This study examined steroidal regulation of tissue factor expression b y cultured endometrial stromal cells. Confluent stromal cell cultures derived from cycling human endometria were exposed to vehicle control, 10(-8) mol/L estradiol (E2), 10(-8)-10(-6) mol/L medroxyprogesterone acetate (MPA), or both E2 and MPA for 2-24 days in serum-containing me dium. The progestin enhanced immunoreactive and functionally active st romal cell tissue factor content, achieving peak effects by 8-12 days of culture. Although E2 alone was ineffective, it augmented MPA-enhanc ed tissue factor content by 8 days of culture, with continued increase s beyond 20 days. Dose-dependent effects on tissue factor protein cont ent were observed between 10(-8)-10(-6) mol/L MPA added alone or toget her with E2. The content of tissue factor mRNA was also increased by M PA and synergistically increased by E2 PIUS MPA. Similar steroidal eff ects on stromal cell tissue factor protein and mRNA content were obser ved using a defined medium. After optimal induction of tissue factor e xpression by E2 plus MPA, removal of these steroids reduced levels of stromal cell tissue factor mRNA and protein, with virtually complete r eversal by day 7 of withdrawal. These time-course and dose-response re lationships establish in vitro conditions with which to dissect factor s controlling endometrial hemostasis, whereas the observed effects of steroid withdrawal establish a novel model for the study of mechanisms regulating normal and abnormal uterine bleeding.