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 17 beta-estradiol, progesterone, and testosterone on secretion of plasminogen activators and plasminogen activator inhibitor type 1 by cultured endothelial cells.


METHODS
Bovine aortic endothelial cells were cultured in medium that contained 17 beta-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 hormones 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 17 beta-estradiol concentration of 10(-12) mol/L (p < 0.03). At higher concentrations of 17 beta-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 17 beta-estradiol or progesterone at a concentration of 10(-12) mol/L and were maximal at 10(-7) mol/L 17 beta-estradiol, progesterone, and testosterone.


CONCLUSIONS
The secretion of plasminogen activators and plasminogen activator inhibitor type 1 is regulated in a biphasic dose-dependent manner by sex hormones in bovine aortic endothelial cells.
Sobel
M I
MI
Department of Obstetrics and Gynecology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Winkel
C A
CA
Macy
L B
LB
Liao
P
P
Bjornsson
T D
TD
D000818:Animals; D001011:Aorta; D015153:Blotting, Western; D002417:Cattle; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology
D017077:Culture Media, Conditioned; D012739:Gonadal Steroid Hormones; D017395:Plasminogen Activator Inhibitor 1; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D010960:Plasminogen Activators