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 serine proteases and matrix metalloproteinases (MMPs), are thought to play important roles in this process. In this study we have examined the regulation of 11 MMPs and 3 tissue inhibitors of metalloproteinases (TIMPs) during gonadotropin-induced ovulation in the mouse. Northern blot hybridization showed 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 contained gelatinolytic activities corresponding to the inactive proforms of gelatinase 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 5-10 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 TIMP-1 messenger RNA were localized to the granulosa and thecal-interstitial cells of large preovulatory and ovulating follicles. This temporal and spatial regulation pattern suggests that MMP-19 might be involved in the tissue degradation that occurs during follicular rupture and that TIMP-1 could have a role in terminating MMP activity after ovulation.
Hägglund
A C
AC
Department of Medical Biochemistry and Biophysics, Umeå University, Sweden.
Ny
A
A
Leonardsson
G
G
Ny
T
T
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005109:Extracellular Matrix / Q000201:enzymology*; D005260:Female; D005498:Follicular Phase / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D006062:Gonadotropins / Q000494:pharmacology*; D006064:Gonadotropins, Equine / Q000494:pharmacology; D008183:Luteal Phase / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000378:metabolism*; D010060:Ovulation / Q000378:metabolism*; D010062:Ovulation Induction; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D006064:Gonadotropins, Equine; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D005780:Gelatin; D008666:Metalloendopeptidases