Drospirenone Effects on the Plasminogen Activator System in Immortalized Human Endometrial Endothelial Cells

Drospirenone (DRSP) is a fourth-generation progestin that interacts with the progesterone receptor (PR) and androgen receptor (AR) in addition to uniquely interacting to the mineralocorticoid receptor (MR). The known effects of DRSP via the mineralocorticoid receptor (MR) are limited. This study seeks to determine if DRSP alters plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in human immortalized endometrial endothelial cells (HEEC) and if such changes in the plasminogen activator system (PAS) are mediated through the MR or AR. The in vitro cell culture experiments utilizing an immortalized human endometrial endothelial cell line evaluated two concentrations of DRSP on PAI-1 and tPA levels in the culture media using specific enzyme-linked immunoassays (ELISA). Experiments adding DRSP with an androgen receptor blocker, flutamide, or a mineralocorticoid receptor agonist, aldosterone, were performed to elucidate which receptor(s) mediated the PAS effects. DRSP 10 μM significantly decreased both HEEC levels of PAI-1 and tPA to 0.75 ± 0.04 and 0.82 ± 0.05 of control, respectively. These direct effects were blunted by flutamide, an AR antagonist. PAI-1 and tPA were not changed by the MR agonist, aldosterone. DRSP significantly decreased both PAI-1 and tPA in the HEECs via the androgen receptor.