PMID- 10770206
OWN - NLM
STAT- MEDLINE
DCOM- 20000501
LR  - 20220409
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 4
DP  - 2000 Apr
TI  - Progesterone exposure prevents matrix metalloproteinase-3 (MMP-3) stimulation by 
      interleukin-1alpha in human endometrial stromal cells.
PG  - 1611-9
AB  - 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.
FAU - Keller, N R
AU  - Keller NR
AD  - Department of Cellular and Molecular Pathology and the Women's Reproductive 
      Health Research Center, Vanderbilt University School of Medicine, Nashville, 
      Tennessee 37232, USA.
FAU - Sierra-Rivera, E
AU  - Sierra-Rivera E
FAU - Eisenberg, E
AU  - Eisenberg E
FAU - Osteen, K G
AU  - Osteen KG
LA  - eng
GR  - HD-28128/HD/NICHD NIH HHS/United States
GR  - HD-30472/HD/NICHD NIH HHS/United States
GR  - U54-HD-37321/HD/NICHD NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Gonanes)
RN  - 0 (Hormone Antagonists)
RN  - 0 (Interleukin-1)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - H6H7G23O3N (onapristone)
SB  - IM
MH  - Adult
MH  - Endometrium/*enzymology
MH  - Female
MH  - Gonanes/pharmacology
MH  - Hormone Antagonists/pharmacology
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Menstrual Cycle
MH  - Organ Culture Techniques
MH  - Pregnancy
MH  - Progesterone/administration & dosage/antagonists & inhibitors/*pharmacology
MH  - Stromal Cells/*enzymology
EDAT- 2000/04/19 00:00
MHDA- 2000/04/19 00:01
CRDT- 2000/04/19 00:00
PHST- 2000/04/19 00:00 [pubmed]
PHST- 2000/04/19 00:01 [medline]
PHST- 2000/04/19 00:00 [entrez]
AID - 10.1210/jcem.85.4.6502 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Apr;85(4):1611-9. doi: 10.1210/jcem.85.4.6502.