CONTROL OF EXTRACELLULAR-MATRIX REMODELING WITHIN OVARIAN TISSUES - LOCALIZATION AND REGULATION OF GENE-EXPRESSION OF PLASMINOGEN-ACTIVATORINHIBITOR TYPE-1 WITHIN THE OVINE CORPUS-LUTEUM

Extensive extracellular matrix remodelling occurs within the lifespan of the corpus luteum, particularly during corpus luteum formation and regression. A major mechanism for the regulation of extracellular matr ix remodelling is via local production of specific proteinase inhibito rs, such as the serine proteinase inhibitor plasminogen activator inhi bitor type-1 (PAI-1). The objective of the present study was to charac terize the localization, ontogeny and regulation of PAI-1 expression w ithin ovine corpora lutea. Urokinase binding activity was detected wit hin medium conditioned by ovine luteal cells. Production of PAI-1 by o vine luteal cells was confirmed by immunoprecipitating it from labelle d proteins in culture medium. mRNA encoding PAI-1 was present within d eveloping (day 3), mature (day 10) and regressing (30 h after prostagl andin F-2 alpha injection on day 10 after the onset of oestrus) corpor a lutea as demonstrated by in situ hybridization. The ontogeny of PAI- 1 mRNA expression was characterized within corpora lutea collected on days 3, 7, 10, 13 and 16 after the onset of oestrus (n = 4, 4, 4, 3 an d 4, respectively). Expression of PAI-1 mRNA did not differ during the luteal phase (P = 0.06), although a trend for an increase in the amou nt of PAI-1 mRNA was observed on day 16. Expression of PAI-1 mRNA was also examined during luteal regression in corpora lutea collected 0, 6 , 12, 24 and 36 h after injection of prostaglandin F-2 alpha on day 10 after the onset of oestrus (n = 4 at each time). Relative PAI-1 mRNA concentrations changed significantly during luteolysis induced by pros taglandin F-2 alpha (P = 0.0002). Administration of prostaglandin F-2 alpha resulted in a transient sevenfold increase in PAI-1 mRNA 6 h aft er injection (P = 0.0001) but by 12 h the amounts had returned to valu es similar to those detected on day 10. We conclude that PAI-1 is a ma jor secretory product of ovine luteal cells and that a transient incre ase in PAI-1 mRNA occurs during luteolysis induced by prostaglandin F- 2 alpha. PAI-1 probably plays a key local role in the control of extra cellular proteolysis during the luteal phase.