Regulation of plasminogem activators and matrix metalloproteinases during development and regression of the corpus luteum in the mouse

Abstract

Proteolysis mediated by plasminogen activators (PAs) and matrix metalloproteinases (MMPs) has been associated with various physiological processes in many organs including the ovary. After ovulation, the ruptured follicle converts to a corpus luteum (CL) in a process that involves active tissue remodeling and angiogenesis The CL is a transient hormone secreting organ that produces progesterone which is required for the maintenance of pregnancy. If no implantation occurs, the CL undergoes regression during which it first loses the ability to produce progesterone and then is structurally degenerated. By using a pseudopregnant mouse model, we have studied and localized the expression of proteases and protease inhibitors during different developmental stages of CL by Northern blot and in situ hybridization analysis. During formation of CL tPA, uPA and PAI-1 as well as stromelysin-3, membrane type MMP (MT1-MMP) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were expressed but with varying expression pattern. In contrast only uPA was expressed during the functional luteal phase. During the late luteal regression the expression of tPA, uPA, stromelysin-3, MT1-MMP and TIMP-1 increased again, which correlated with an increased apoptosis as determined by in situ 3'-end labeling. Our data demonstrate that proteases and protease inhibitors are coordinately and temporally expressed during formation and regression of corpus luteum. The tumor related metalloproteinases stromelysin3 and MT1-MMP exhibit normal physiological expressions during this processes. The expression pattern indicate that uPA may play a role during the functional phase. Studies with gene deficient mice that are in progress will reveal the functional role of proteases during the developmental cycle of CL.