Estrogen Regulation of a Tissue Factor-Like Procoagulant in the Immature Rat Uterus*

Abstract

An estrogen-responsive procoagulant activity is present in the plasma membrane fraction of immature rat uterus. This procoagulant has many of the properties of tissue factor, a widely occurring, integral membrane protein which initiates the intrinsic pathway of coagulation. Procoagulant activity was demonstrated to activate prothrombin in rat uterus, to activate human coagulation factor X, and to cause clot formation by human plasma. Procoagulant activity could be solubilized from the plasma membrane by the detergent octyl glucoside and had an apparent mol wt of 20,000-40,000 by gel filtration. Procoagulant activity was increased 4-fold within 3 h after immature rats were injected with estradiol. The increase was tissue- and hormone specific and was not affected by a warfarin-induced vitamin K deficiency. Coagulation factor VII was required for clot formation by the procoagulant. These properties are consistent with identification of the procoagulant as tissue factor. mRNA for tissue factor was increased in the uterus 3 h after estrogen stimulation. In the preceding paper we showed that prothrombin is increased in the immature uterus within 3 h of estrogen stimulation. The presence of increased amounts of a tissue factor-like procoagulant in the same time period suggests a functional relationship between these two proteins and a possible role for both in uterine development. Thrombin is a growth factor in fibroblasts and endothelial cells. We propose that after estrogen stimulation, prothrombin enters the uterus with the influx of plasma proteins and is activated by the procoagulant to thrombin. We suggest that thrombin might act as a paracrine factor early in the estrogen-stimulated development of the uterus.