The regulation of plasminogen activators and plasminogen activator inhibitor type 1 in endothelial cells by sex hormones,

OBJECTIVE: The purpose of this study was to assess the effect of 17β-estradiol, progesterone, and testosterone on secretion of plasminogen activators and plasminogen activator inhibitor type 1 by cultured endothelial cells. STUDY DESIGN: Bovine aortic endothelial cells were cultured in medium that contained 17β-estradiol, progesterone, or testosterone at various concentrations (10−13 to 10−6 mol/L). Plasminogen activator activity in culture medium in the presence of cells was assayed after a 36-hour incubation using chromogenic substrate and iodine 125-labeled fibrin plate assays. Plasminogen activator inhibitor type 1 antigen was detected in conditioned media of bovine aortic endothelial cells by Western blotting analysis. RESULTS: All three steroid hormone exhibited biphasic dose-response effects, characterized by stimulation of plasminogen activator secretion at lower concentrations and inhibition of plasminogen activator secretion at higher concentrations. A significant stimulatory effect on plasminogen activator secretion (74% over control) was observed at a 17β-estradiol concentration of 10−12 mol/L (p< 0.03). At higher concentrations of 17β-estradiol, progesterone, and testosterone, inhibition of plasminogen activator secretion was observed (p< 0.05). Decreased levels of plasminogen activator inhibitor type 1 antigen were detected in supernatants treated with either 17β-estradiol or progesterone at a concentration of 10−12 mol/L and were maximal at 10−7 mol/L 17β-estradiol, progesterone, and testosterone. CONCLUSION: The secretion of plasminogen activators and plasminogen activator inhibit type 1 is regulated in a biphasic dose-dependent manner by sex hormones in bovine aortic endothelial cells.