Plasminogen activator/plasminogen activator inhibitors in ovarian physiology.

The target extracellular matrix (ECM) degradation generated by plasminogen activator (PA) and regulated by plasminogen activator inhibitor (PAI) is an event that affects a wide variety of physiological and pathological processes in the ovary. Studies carried out over the past 25 years in a number of laboratories have elucidated some of the biochemical events related to the function and regulation of the PA system in the ovary. Hormone-induced coordinated expression of tissue-type PA (tPA) produced mainly by granulosa cells and its inhibitor PAI-1 secreted by theca cells in the preovulatory follicles is responsible for a controlled and directed proteolysis leading to the rupture of selected follicles in the rat, monkey and other mammals. Increase in tPA and PAI-1 expression in corpus luteum (CL) of rat and monkey at a later stage is well correlated with a sharp decrease in CL progesterone production, indicating its important role in the initiation of luteal regression. In contrast, the urokinase-type PA (uPA) may play an essential role in the early growing follicles during cell proliferation and migration, and in the early CL formation related to ECM degradation and angiogenesis. Ovarian function is also modulated by endogenously-produced local factors that regulate expression of the PA activator and inhibitor, and the MMP system. Thus, the next challenge is to identify the interrelationship between multiple paracrine and autocrine factors and the PA system, and to know how they regulate the protease and the protease inhibitor in the ovary.