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

The distribution of gelatinases/matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) ill neonatal and gonadotropin-primed immature rat ovaries was studied by immunofluorescent microscopy. Immature female Long-Evans rats were primed with 15 IU pregnant mare's serum gonadotropin (PMSG) in 100 mu l PBS. Two days later, to induce ovulation, the rats were injected with human chorionic gonadotropin (hCG, 5 IU/100 mu l PBS). The animals were killed at appropriate times and the ovaries removed and processed for cryostat or paraffin sectioning. Ovaries were also obtained from 7-day-old neonatal rats and processed as above. In the neonatal rat ovary, MMP-2 was present in the follicle and in the ovarian surface epithelium. MMP-9 was not detectable in the neonatal ovary. TIMP-1 was present in the oocyte and in the surface epithelium. In the PMSG-primed ovary, MMP-2 was present in the granulosa and thecal cells of the ovary. MMP-9 distribution, however, was restricted to the interstitial and thecal cells. TIMP-1 was mainly present in the blood vessels and thecal cells, with minor staining in the granulosa cells. In the developing corpus luteum, luteal and endothelial cells were positive for MMP-2. MMP-9 localization was restricted to the plasma membrane of the luteal and interstitial cells. TIMP-1 was clearly observed in the luteal capillaries and, to a lesser extent, in the luteal cell plasma membrane. This distribution of MMP-2, MMP-9, and TIMP-1 in the corpus luteum persisted throughout the life span of the corpus luteum. The spatial and temporal distribution of the gelatinases and TIMP-1 suggests unique roles for these proteins in the rat ovary.