Collagenase, Gelatinase, and Proteoglycanase Messenger Ribonucleic Acid Expression and Activity during Luteal Development, Maintenance, and Regression in the Pseudopregnant Rat Ovary1

Abstract

In the present study, we examined the roles of the matrix metalloproteinases collagenase, 72-kDa and 92-kDa gelatinase, and proteoglycanase in the tissue remodeling that occurs during luteal development and regression, using a pseudopregnant rat model. Pseudopregnancy was induced in immature female rats by eCG/hCG priming, and animals (n = 3 to 4 per time point) were killed on Days 1, 2, 4, 8, 12, 14, or 16 of pseudopregnancy (Day 0 = time of hCG administration). Ovaries were then removed and analyzed for either matrix metalloproteinase mRNA expression or activity. During luteal development (Day 1 of pseudopregnancy), activity of both collagenase (p = 0.009) and gelatinase (p = 0.0003), but not proteoglycanase (p > or = 0.05), was significantly greater than at all other time points. In accord with gelatinase activity, transcript levels of this enzyme were elevated at Day 1 of pseudopregnancy. Specifically, gelatinase transcript levels for the 72-kDa 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 reached 10-fold lower levels by Days 8 and 12 of pseudopregnancy. Proteoglycanase transcript could not be detected by Northern analysis during luteal development or any other time point examined in the current study. During the period of luteal maintenance (approximately Days 4-8 of pseudopregnancy in the rat), collagenase and gelatinase displayed basal levels of activity, but only proteoglycanase activity was elevated compared to luteal development levels of this enzyme. During luteal regression (Days 12-14 of pseudopregnancy in the rat), all enzymes displayed basal levels of enzyme activity. In accord with gelatinolytic activity during luteal regression, both 72-kDa and 92-kDa gelatinase mRNA were detectable at baseline levels. In contrast to the baseline levels of collagenolytic activity during luteal regression, collagenase transcript displayed peak values (approximately 8-fold greater than Day 1 levels; p = 0.004) at Day 12 of pseudopregnancy. It is concluded from these studies that collagenase and the gelatinases play a role in the tissue remodeling associated with luteal development, proteoglycanase is associated with luteal maintenance, and collagenase may contribute to the structural regression of the corpus luteum.

Differential distribution of gelatinases and tissue inhibitor of metalloproteinase-1 in the rat ovary

“…Its expression in the luteal cell membrane, however, suggests that MMP-9 may be essential for the organization of these cells in the corpus luteum. This is consistent with the observation that this metalloproteinase transcript is highly expressed on day 1 of pseudopregnancy (Nothnick et al 1996). Further, the compartment-specific expression of MMP-9 may be related to the expression of interleukin-1 in the ovary.…”

Expression of an extracellular matrix metalloproteinase inducer (basigin) in the human ovary and ovarian endometriosis

“…Gelatinolytic activity patterns (assessed by zymography in the rat and human) correlate spatially and temporally with our characterization of luteal basigin expression (27)(28)(29)(30). In particular, MMP-9 activity was elevated in human CL during the early luteal phase (31).…”

Matrix Metalloproteinases and Their Tissue Inhibitors in the Developing Neonatal Mouse Uterus1

“…Zymography was conducted using previously described methods with a few modifications [25,26]. All zymographic studies were performed using three pools of uteri from for each PND (n ϭ 3).…”