title: Progesterone exposure prevents matrix metalloproteinase-3 (MMP-3) stimulation by interleukin-1alpha in human endometrial stromal cells.
abstract: Suppression of endometrial matrix metalloproteinases (MMPs) is necessary to maintain tissue stability during the invasive events of implantation and placental development. Several laboratories have shown that inflammatory cytokines, including interleukin-lalpha (IL-1alpha), can oppose progesterone suppression of MMPs in the human endometrium. Furthermore, we have recently demonstrated colocalization of epithelial cell IL-1alpha and MMP-7 expression at sites of ectopic pregnancy. The current study extends these findings, revealing a previously unrecognized interrelationship between progesterone and IL-1alpha in regulation of MMP-3. Although IL-1alpha is a potent stimulator of MMP-3 in proliferative phase endometrium in organ culture, we demonstrate that progesterone exposure in vivo reduces IL-1alpha stimulation of MMP-3 in secretory phase tissue. This loss of sensitivity to IL-1alpha was duplicated in isolated stromal cells treated with progesterone in vitro, and IL-1alpha stimulation of MMP-3 returned in a dose-dependent manner with progesterone withdrawal. The antiprogestin, onapristone, partially blocked the ability of progesterone to prevent stimulation of MMP-3 by IL-1alpha. These data suggest a novel mechanism by which progesterone may preserve tissue integrity during the establishment and maintenance of pregnancy by limiting stimulation of MMPs by inflammatory cytokines such as IL-1a.
authors.affiliation: Department of Cellular and Molecular Pathology and the Women's Reproductive Health Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Keller
authors.forename: E
authors.initials: E
authors.lastname: Sierra-Rivera
authors.forename: E
authors.initials: E
authors.lastname: Eisenberg
authors.forename: K G
authors.initials: KG
authors.lastname: Osteen
mesh_terms: D000328:Adult; D004717:Endometrium / Q000201:enzymology*; D005260:Female; D006067:Gonanes / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008597:Menstrual Cycle; D009924:Organ Culture Techniques; D011247:Pregnancy; D011374:Progesterone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017154:Stromal Cells / Q000201:enzymology*
chemical_list: D006067:Gonanes; D006727:Hormone Antagonists; D007375:Interleukin-1; D011374:Progesterone; D019278:Matrix Metalloproteinase 3; C053238:onapristone