| 16967517 |
Zhang X, Christenson LK, Nothnick WB: Regulation of MMP-9 expression and activity in the mouse uterus by estrogen. Mol Reprod Dev. 2007 Mar;74(3):321-31.
Matrix metalloproteinases (MMPs) are spatiotemporally expressed in the uterus across normal estrous and menstrual cycles and are known to participate in the extensive endometrial tissue remodeling. MMP-9/gelatinase B is one of the major MMPs found in the uterus that modulates uterine biology during various reproductive processes. Although it seems that uterine MMP-9 is under ovarian steroid hormonal control, there are conflicting reports regarding steroidal hormonal regulation of MMP-9 expression, and there is little information on the effects of estrogen in vivo in this respect. We therefore examined the steroidal regulation of MMP-9 within the mouse uterus. Female mice (2-3 months old) were ovariectomized and treated with estradiol-l7beta (E (2)) or E (2) + progesterone (P (4)) and uterine gelatinase activity and expression were determined. Gelatin zymography revealed that E (2) alone or in combination with P (4) increased MMP-9 activation, whereas Northern analysis showed that E (2) decreased MMP-9 steady state mRNA expression and an estrogen receptor antagonist ICI-182, 780 blocked this effect. In contrast, uterine MMP-2 expression and activity were not affected by steroidal treatments. Pretreatment with a transcription inhibitor actinomycin D or translation inhibitor cycloheximide indicates that E (2) regulates uterine MMP-9 at multiple points, involving transcriptional and posttranscriptional control as well as modulation of inhibitor activities. Collectively, these data suggest that E (2) regulates uterine MMP-9 expression and activity in vivo via a complex mechanism. This estrogen regulation of MMP-9 activity may play an important role in uterine tissue remodeling. |
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