PGE2 REGULATES THE PLASMINOGEN ACTIVATOR PATHWAY IN HUMAN ENDOMETRIAL ENDOTHELIAL CELLS: DIFFERENCES BETWEEN NORMAL AND HEAVY MENSTRUAL BLEEDERS

Abstract

This study seeks to determine if Prostaglandin E2 (PGE2) alters plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in human endometrial endothelial cells (HEEC) and identify any differences between women with normal and heavy menstrual bleeding. HEEC primary cultures were established from two groups of women: heavy menstrual bleeding (HMB, n=2), and normal menstrual bleeding (NMB, n=3). HEEC were cultured with PGE2 at concentrations of 10-7 10-9, 10-11 M and no PGE2 as a control. We used ELISAs to assess the concentration of PAI-1 and tPA in media; total protein was extracted from the cells and determined using the Bicinchoninic Acid protein assay. There were no differences in patient demographics, the average age in NMB 27.7 and HMB was 31.2 (p=0.44). HMB women had at least one fibroid by ultrasound. There was an increase in PAI-1 concentration in HEEC exposed to both 10-7 and 10-9 M of PGE2 in NMB, 332 ±183 and 248-±70 % of control, respectively. HMB women had a different outcome with PAI-1 where concentrations decreased 68 ±29 and 59-±22 % of control at both 10-7 and 10-9 M of PGE2, respectively. There was no change in tPA concentration 111 ±43 and 103±19% of control in NMB at 10-7 and 10-9 M of PGE2, respectively, but a decrease in tPA concentration when PGE2 was added to the cell cultures of HMB women, 68 ±4, and 64 ±16 % control with 10-9 and 10-11 M of PGE2 respectively (Table 1). PGE2 increased PAI-1 concentration in endothelial cells of NMB, which would lead to more stable clots during menses and an objectively lighter menses. PAI-1 secretion from endothelial cells of HMB women did not respond. This suggests that the endothelium of HMB women may be dysregulated in their PAI-1/tPA pathway in response to PGE2, which may be a central cause of their heavier menses.