COORDINATED EXPRESSION OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 DURING CORPUS-LUTEUM FORMATION AND LUTEOLYSIS IN THE ADULT PSEUDOPREGNANT RAT

Proteolytic activity generated by the plasminogen activator (PA) syste m is associated with many biological processes, Using an adult pseudop regnant rat model we have studied how two components of the PA system, tissue-type plasminogen activator (tPA) and plasminogen activator inh ibitor type 1 (PAI-1), are expressed temporally and spatially during d ifferent developmental stages of the corpus luteum (CL). Northern blot analysis, in situ hybridization, in situ zymography, and fibrin overl ay were used to analyze the expression and distribution of tPA and PAI -1 messenger RNA (mRNA) as well as PA activity in CL of different ages . We demonstrated that during the luteinization period (approximately days 1-2), tPA mRNA was highly and evenly expressed in newly formed CL , whereas PAI-1 mRNA was mainly detected in the central part of the sa me CL. In accordance with these findings, proteolytic activity generat ed by tPA was detected in the outer region of newly formed CL by in si tu zymography. During the luteotropic period (approximately days 3-10) , tPA mRNA expression was very low. PAI-1 mRNA expression was also low , but increased on day 10. As expected, proteolytic activity was very low during this period. During functional luteolysis (days 13-14) and subsequent structural luteolysis, tPA mRNA was elevated. PAI-1 mRNA wa s also expressed during this period. Moreover, the net PA activity, as determined by fibrin overlay, was relatively high during this period. Our studies indicate that tPA and PAI-1 are coordinately expressed in the CL, resulting in increased proteolytic activities during the lute inization and luteolytic periods. PA-mediated proteolysis may, therefo re, play a role in both CL formation and luteolysis in rats.