title: Regulation of MMP-9 expression and activity in the mouse uterus by estrogen.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Kansas School of Medicine, Kansas City, Kansas 66160, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Lane K
authors.initials: LK
authors.lastname: Christenson
authors.forename: Warren B
authors.initials: WB
authors.lastname: Nothnick
mesh_terms: D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D018093:Gelatinases / Q000378:metabolism; D005786:Gene Expression Regulation; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D004967:Estrogens; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003609:Dactinomycin; D011374:Progesterone; D003513:Cycloheximide; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9