Document Detail


Progesterone exposure prevents matrix metalloproteinase-3 (MMP-3) stimulation by interleukin-1alpha in human endometrial stromal cells.
MedLine Citation:
PMID:  10770206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
N R Keller; E Sierra-Rivera; E Eisenberg; K G Osteen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  85     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2000 Apr 
Date Detail:
Created Date:  2000-05-01     Completed Date:  2000-05-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1611-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Cellular and Molecular Pathology and the Women's Reproductive Health Research Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Endometrium / enzymology*
Female
Gonanes / pharmacology
Hormone Antagonists / pharmacology
Humans
Interleukin-1 / pharmacology*
Matrix Metalloproteinase 3 / metabolism*
Menstrual Cycle
Organ Culture Techniques
Pregnancy
Progesterone / administration & dosage,  antagonists & inhibitors,  pharmacology*
Stromal Cells / enzymology*
Grant Support
ID/Acronym/Agency:
HD-28128/HD/NICHD NIH HHS; HD-30472/HD/NICHD NIH HHS; U54-HD-37321/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Gonanes; 0/Hormone Antagonists; 0/Interleukin-1; 57-83-0/Progesterone; 96346-61-1/onapristone; EC 3.4.24.17/Matrix Metalloproteinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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