Plasminogen Activator in Mouse Uterine Fluid

Abstract

The widespread use of estrogens and pro-gestationals and their possible relationship to thromboembolic phenomena(l) lends special significance to biologic observations establishing a relationship between hormones and coagulation or fibrinolytic systems. Our studies show that female sex hormones suppress an activator of plasminogen in mouse endometrial fluid and thereby inhibit its fibrinolytic activity.

Increased fibrinolytic activity of blood and tissues is due to increased levels of plasminogen activator(2). A great variety of stimuli cause an increase in blood plasminogen activator activity(2). It is less clear what factors increase or suppress tissue activator activity. Human and animal endometrial tissue extracts are particularly rich in a plasminogen activator (3,4). Several investigations suggest a relationship between circulating concentrations of female sex hormones and endometrial plasminogen activator activity. Fibrinolytic activity of the endo-metrium varies during the menstrual cycle, and is absent before menarche and after menopause (3-6). In castrated rats treated with estrogens, an increase in endometrial fibrinolytic activity correlates with falling blood levels of estmgens(5).

An activator of human and bovine plasminogen has been described in the sterile mouse uterine fluid accumulating following cervical ligation(7). This activator is stable at —20°C, and is destroyed by heating to 70°C for 30 minutes at neutral pH. The following experiments demonstrate that estradiol and progesterone given to mice during the accumulation of uterine fluid affect its chemical composition and suppress uterine plasminogen activator activity.

Methods. Bio-Swiss mice underwent cervical ligation as previously described(8). Three groups of 10-12 mice each received either subcutaneous injection of 1 μg estradiol benzoate in 0.1 ml sesame oil daily, or implantation of a pellet containing progesterone acetate from which approximately 0.5 to 1.0 mg was absorbed daily. A control group received sesame oil alone.