COLLAGENASE, GELATINASE, AND PROTEOGLYCANASE MESSENGER-RIBONUCLEIC-ACID EXPRESSION AND ACTIVITY DURING LUTEAL DEVELOPMENT, MAINTENANCE, ANDREGRESSION IN THE PSEUDOPREGNANT RAT OVARY

In the present study, we examined the roles of the matrix metalloprote inases collagenase, 72-kDa and 92-kDa gelatinase, and proteoglycanase in the tissue remodeling that occurs during luteal development and reg ression, using a pseudopregnant rat model, Pseudopregnancy was induced in immature female rats by eCG/hCG priming, and animals (n = 3 to 4 p er time point) were killed on Days 1, 2, 4, 8, 12, 14, or 16 of pseudo pregnancy (Day 0 = time of hCG administration). Ovaries were then remo ved and analyzed for either matrix metalloproteinase mRNA expression o r activity. During luteal development (Day 1 of pseudopregnancy), acti vity of both collagenase (p = 0.009) and gelatinase (p = 0.0003), but not proteoglycanase (p greater than or equal to 0.05), was significant ly greater than at all other time points. In accord with gelatinase ac tivity, transcript levels of this enzyme were elevated at Day 1 of pse udopregnancy. Specifically, gelatinase transcript levels for the 72-kD a and 92-kDa enzymes were greatest at Day 1 (p = 0.0003 and p = 0.001, respectively), decreased 3-fold by Day 2, 4-fold by Day 4, and reache d 10-fold lower levels by Days 8 and 12 of pseudopregnancy. Proteoglyc anase transcript could not be detected by Northern analysis during lut eal development or any other time point examined in the current study. During the period of luteal maintenance (approximately Days 4-8 of ps eudopregnancy in the rat), collagenase and gelatinase displayed basal levels of activity, but only proteoglycanase activity was elevated com pared to luteal development levels of this enzyme, During luteal regre ssion (Days 12-14 of pseudopregnancy in the rat), all enzymes displaye d basal levels of enzyme activity. In accord with gelatinolytic activi ty during luteal regression, both 72-kDa and 92-kDa gelatinase mRNA we re detectable at baseline levels. In contrast to the baseline levels o f collagenolytic activity during luteal regression, collagenase transc ript displayed peak values (approximately 8-fold greater than Day 1 le vels; p = 0.004) at Day 12 of pseudopregnancy. It is concluded from th ese studies that collagenase and the gelatinases play a role in the ti ssue remodeling associated with luteal development, proteoglycanase is associated with luteal maintenance, and collagenase may contribute to the structural regression of the corpus luteum.