Regulation and localization of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the mouse ovary during gonadotropin-induced ovulation

At the time of ovulation, proteolytic degradation of the follicular wall is required to release the mature oocyte. Extracellular proteases, such as se rine proteases and matrix metalloproteinases (MMPs), are thought to play im portant roles in this process. In this study we have examined the regulatio n of 11 MMPs and 3 tissue inhibitors of metalloproteinases (TIMPs) during g onadotropin-induced ovulation in the mouse. Northern blot hybridization sho wed that messenger RNA for several MMPs and TIMPs, including gelatinase A, MT1-MMP, stromelysin-3, MMP-19, TIMP-1, TIMP-2, and TIMP-3, were present at detectable levels in the mouse ovary. In addition, ovarian extracts contai ned gelatinolytic activities corresponding to the inactive pro-forms of gel atinase A and gelatinase B. Most of the MMPs and TIMPs were expressed at a constitutive level throughout the periovulatory period. However, MMP-19 and TIMP-1 revealed a different expression pattern; they were both induced 5-1 0 times by hCG and reached their maximum levels at 12 h after hCG treatment , corresponding to the time of ovulation. At this time point, MMP-19 and TI MP-1 messenger RNA were localized to the granulosa and thecal-interstitial cells of large preovulatory and ovulating follicles. This temporal and spat ial regulation pattern suggests that MMP-19 might be involved in the tissue degradation that occurs during follicular rupture and that TIMP-1 could ha ve a role in terminating MMP activity after ovulation.