The amount and activity of active matrix metalloproteinase 13 is suppressed by estradiol and progesterone in human pelvic floor fibroblasts.
As a key degrader of fibrillar collagens, matrix metalloproteinase 13 (MMP13), may contribute to the progression of pelvic organ prolapse. Here we aimed to define the regulation of MMP13 by estradiol and progesterone in the vaginal supportive tissues. Fibroblasts cultured from the arcus tendineous fasciae pelvis of three pre- and three postmenopausal women with prolapse were treated with 17-beta-estradiol (E2), progesterone (P4), E2 + P4, or E2 + ICI 182,780 (ICI). Collagenase inhibitor I (CI) and MG-132 were employed to investigate the mechanism of MMP13 degradation into inactive fragments (fragmentation) by hormones. The regulation of MMP13 in vivo was assessed by comparing tissues of ovariectomized (ovx) vs. sham-operated rats. Expression of MMP13 (proenzyme and active and fragment forms) was quantitated by Western immunoblotting, and MMP13 enzymatic activity was measured using a substrate degradation assay. The amount of cellular active MMP13 and MMP13 proteolytic activity decreased in the presence of hormones. The decrease was paralleled by increased proenzyme and fragment forms. MG-132, not CI, suppressed cellular MMP13 fragmentation. Active MMP13 increased in rats following ovx and was suppressed by E2 + P4 supplementation. Active MMP13 is suppressed in vivo and in vitro by estradiol and progesterone, suggesting a protective effect against vaginal supportive tissue deterioration.
Zong
Wenjun
W
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Meyn
Leslie A
LA
Moalli
Pamela A
PA
D000290:Adnexa Uteri / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D010052:Ovariectomy; D017773:Pelvic Floor; D017698:Postmenopause; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D014596:Uterine Prolapse / Q000378:metabolism / Q000473:pathology
D061965:Matrix Metalloproteinase Inhibitors; D011374:Progesterone; D004958:Estradiol; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13