Differential Release of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases by Human Granulosa-Lutein Cells and Ovarian Leukocytes

Tissue reorganization during ovulation and corpus luteum formation involves a coordinated action of matrix metalloproteinases ( MMPs) and tissue MMP inhibitors (TIMPs). In this study we investigated the cellular source of ovarian MMPs and TIMPs. Cells isolated from the preovulatory human follicle were cultured after immunobead depletion of CD45-expressing cells, which allowed differential assessment of leukocyte and granulosa-lutein cell fractions. Secretion of MMP-9 by follicular fluid-derived cells was associated with the presence of leukocytes. Granulosa-lutein cells synthesized low levels of MMP-9 but failed to secrete this enzyme that presumably accumulated in the cytoplasm, indicated by an increased MMP-9 expression of luteinized cells in sectioned midluteal phase corpora lutea. Synthesis and secretion of TIMP by follicular fluid-derived cells was associated with granulosa-lutein cells. TIMPs derived by granulosa-lutein cells failed to inhibit MMP-related pericellular proteolysis. The findings support a two-cell model of periovulatory MMP/TIMP release, in which leukocytes secreteMMPsandgranulosa-lutein cells release TIMP, suggesting that there exists an intriguing interaction among cells that intertwingle during ovulation and corpus luteum formation. (Endocrinology 151: 1290-1298, 2010)