Regulation of plasminogen activator in rat endometrial stromal cells: The role of epidermal growth factor

The effect of epidermal growth factor (EGF) on the accumulation of plasminogen activator (PA) activity in the medium of cultured rat endometrial stromal cells isolated from uteri sensitized for the decidual cell reaction was examined. Treatment with EGF increased, in a concentration-dependent manner, PA activity in the medium. This effect was inhibited or greatly reduced by inhibitors of transcription and translation. Incubation of the cells with prostaglandin E₂ increased PA activity in the medium. Indomethacin, which inhibited prostaglandin accumulation in the medium, slightly but significantly decreased the EGF-induced increase in PA activity in the medium. As indicated by zymography and the use of amiloride in the PA assay, the activity in the medium was primarily urokinase-type plasminogen activator (uPA). Finally, EGF caused an increase in the steady-state uPA mRNA levels in the cells. These results provide evidence that EGF causes an increase in the secretion of uPA by rat endometrial stromal cells from uteri sensitized for the decidual cell reaction through a mechanism that involves an increase in steady-state uPA mRNA levels.