Regulation of the Plasminogen Activator System in the Ovary

Abstract

Extracellular matrix (ECM) not only provides a structural support for the organism, but also actively conducts cell-to-cell signal transduction and regulates cell proliferation, migration, development and metabolism. The targeted ECM degradation generated by plasminogen activator (PA) and regulated by plasminogen activator inhibitor (PAI) is, therefore, an event that affects a wide variety of physiological and pathological processes. The ovary is the best model to study the regulation and function of extracellular proteolysis mediated by multicomponents like the PA system. Studies carried out over the past 10 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 proteolytic activity provided by tissue-type PA(tPA) and modulated by PAI-1 in the preovulatory follicles is responsible for a controlled and directed proteolysis leading to rupture of selected follicles during ovulation, whereas the coordinated expression of urokinase-type PA (uPA) and PAI-1 in the early growing follicle may be important in ECM degradation during cell proliferation and migration; the PA system may also play a role in the control of corpus luteum (CL) development through an autocrine or paracrine mechanism. Increase in tPA and PAI-1 expression in CL at a later stage is well correlated with a sharp decrease in CL progesterone production, while the increase in uPA mRNA levels and activity in the early stage of CL development is correlated with an increase in progesterone secretion.

The prevalence of 4G5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in polycystic ovarian syndrome and its association with plasma PAI-1 levels

“…Since there are data to suggest that PAI-1 is involved in luteolysis, modifying the reproductive potential, it could be intriguing to speculate on a dual role of elevated levels of PAI-1 in PCOS (22,23). In conclusion, the PCOS women had higher PAI-1 levels compared with the control group.…”

Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries

“…This releases active NF-B protein from cytoplasmic retention signals and allows it to translocate to the nucleus and activate numerous target genes (Karin and Ben Neriah 2000;Read et al 2000). AGE-RAGE signaling through NF-B activation has been reported to regulate expression of inXammatory cytokines (such as TNF-and interleukin-1) (Singh et al 2001), PAI-1 (Diamanti-Kandarakis et al 2004) and endothelin-1 (Diamanti-Kandarakis et al 2001), molecules that have also been found to be elevated in women with PCOS and are linked with endothelial dysfunction and vascular damage as well as with dysregulation of the ovulatory process (Glueck et al 1999;Liu 1999).…”

Localization and Expression of Messenger RNAs for the Peroxisome Proliferator-Activated Receptors in Ovarian Tissue from Naturally Cycling and Pseudopregnant Rats1

“…Another protease, stromelysin, has a PPRE in its promoter region [6], suggesting that expression of this protease is also regulated by PPARs. These proteases have been identified in ovarian and/or luteal tissue from various species (for review, see [12,13]), indicating that PPARs could regulate protease activity and influence luteal formation and/or regression. In addition, activation of PPAR␥ has been shown to inhibit angiogenesis both in vitro and in vivo [5].…”