The family of matrix metalloproteinases appears to be involved in physiologic and pathologic processes associated
with extracellular matrix remodeling such as those that occur in embryonic development, tissue repair, and tumor
progression. Stromelysin III, a member of this gene family, is overexpressed in the stromal cells of
invasive breast carcinomas but not in the stromal cells surrounding benign breast fibroadenomas. Stromelysin III is also called matrix metalloproteinase-11, or MMP11.
General function
Enzyme, Hydrolase, Peptidase/Protease
Comment
Cellular localization
Secreted
Comment
Ovarian function
Follicle atresia, Oogenesis, Oocyte maturation
Comment
Ovarian Expression and Regulation of the Stromelysins During the Periovulatory Period in the Human and the Rat. McCord LA et al. The matrix metalloproteinases (MMPs) are postulated to facilitate follicular rupture. In the present study, expression of the stromelysins (MMP3, MMP10, MMP11) was analyzed in the periovulatory human and rat ovary. Human granulosa and theca cells were collected from the dominant follicle at various times after hCG. Intact rat ovaries, granulosa cells, and residual tissue (tissue remaining after granulosa cell collection) were isolated from eCG-hCG-primed animals. Mmp10 mRNA was highly induced in human granulosa and theca cells and intact rat ovaries, granulosa cells, and residual tissue. Localization of MMP10 to granulosa and theca cells in both human and rat ovarian follicles was confirmed by immunohistochemistry. Mmp3 mRNA was unchanged in human cells and rat granulosa cells but increased in intact rat ovaries and residual tissue. Mmp11 mRNA decreased following hCG treatment in human granulosa and theca cells as well as rat granulosa cells. Regulation of Mmp10 in cultured rat granulosa cells revealed that the EGF inhibitor AG1478 and the progesterone antagonist RU486 suppressed the induction of Mmp10 mRNA whereas the prostaglandin inhibitor NS398 had no effect. Studies on the Mmp10 promoter demonstrated forskolin plus PMA stimulated promoter activity, which was dependent upon a proximal AP1 site. In conclusion, there are divergent patterns of stromelysin expression associated with ovulation with a marked induction of Mmp10 mRNA, a decrease in Mmp11 mRNA, yet a species dependent pattern on Mmp3 mRNA expression. The induction of Mmp10 expression suggests an important role for this MMP in the follicular changes associated with ovulation and subsequent luteinization.
Hagglund AC, et al reported that stromelysin-3 Is Induced in Mouse Ovarian Follicles Undergoing
Hormonally Controlled Apoptosis, but This Metalloproteinase Is
Not Required for Follicular Atresia.
They have investigated the expression pattern
and functional role of the matrix metalloproteinase stromelysin-3 in follicular
atresia. Twenty-four hours after the treatment of immature female mice with a low
dose of eCG, both apoptosis and the stromelysin-3 mRNA expression were
suppressed approximately threefold. However, the initial suppression of
apoptosis and stromelysin-3 expression was followed by a time-dependent
increase, and 96 h after eCG treatment, the levels were similar to those of
untreated control mice. In 15- to 16-day-old juvenile mice, the ovary consisted of
relatively undeveloped follicles, and almost no apoptosis and only low
stromelysin-3 mRNA expression were observed. However, at the age of 21 days,
when several antral follicles were present, a fivefold induction in both apoptosis
and stromelysin-3 mRNA expression was detected. For both models, in situ
analysis revealed that the expression of stromelysin-3 mRNA was localized to the
granulosa cells of atretic follicles.
Gene whose expression is detected by cDNA array hybridization: oncogenes, tumor
suppressors, cell cycle regulators Rozenn Dalbi?Tran and Pascal Mermilloda
Expression regulated by
FSH
Comment
Ovarian localization
Granulosa
Comment
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: To address the functional role of stromelysin-3
in follicular atresia, stromelysin-3-deficient mice were studied Hagglund AC, et al . However, no
difference in the pattern of apoptotic DNA fragmentation and no apparent
morphological differences were observed when ovaries from wild-type and
stromelysin-3-deficient mice were compared. Thus, stromelysin-3 is induced during follicular atresia, but that this protease is not
obligatory for initiation or completion of the atretic process.