Document Detail

Regulation and function of LEFTY-A/EBAF in the human endometrium. mRNA expression during the menstrual cycle, control by progesterone, and effect on matrix metalloprotineases.
MedLine Citation:
PMID:  12215426     Owner:  NLM     Status:  MEDLINE    
The human endometrium is a unique tissue that is periodically shed during menstruation. Although overall triggered by ovarian steroids withdrawal, menstrual induction of matrix metalloproteinases (MMPs) and resulting tissue breakdown are focal responses, pointing to additional local modulators. LEFTY-A, a novel member of the transforming growth factor-beta family identified originally as an endometrial bleeding-associated factor (EBAF), is a candidate for this local control. We measured LEFTY-A and beta-ACTIN mRNA concentration during the menstrual cycle in vivo and found that their ratio was dramatically ( approximately 100-fold) increased at the perimenstrual phase. A similar increase was seen when proliferative explants were cultured for 24 h in the absence of ovarian steroids; this was followed by spontaneous production of proMMP-1, -3, and -9. Both responses were inhibited by progesterone. Moreover, addition of recombinant LEFTY-A to proliferative explants was sufficient to stimulate the expression of proMMP-3 and -7; this response was also blocked by ovarian steroids. Collectively, these data indicate that LEFTY-A may provide a crucial signal for endometrial breakdown and bleeding by triggering expression of several MMPs. Progesterone appears to exert a dual block, upstream by inhibiting LEFTY-A expression and downstream by suppressing its stimulatory effect on MMPs.
Patricia B Cornet; Christine Picquet; Pascale Lemoine; Kevin G Osteen; Kaylon L Bruner-Tran; Siamak Tabibzadeh; Pierre J Courtoy; Yves Eeckhout; Etienne Marbaix; Patrick Henriet
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2002-09-04
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  277     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-11-04     Completed Date:  2003-02-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  42496-504     Citation Subset:  IM    
Cell Biology Unit, Christian de Duve Institute of Cellular Pathology, Université catholique de Louvain, Avenue Hippocrate, 75, B-1200 Bruxelles, Belgium.
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MeSH Terms
Actins / metabolism
Base Sequence
DNA Primers
Endometrium / drug effects,  physiology*
Gene Expression Regulation* / drug effects
Left-Right Determination Factors
Matrix Metalloproteinases / metabolism*
Menstrual Cycle / physiology*
Organ Culture Techniques
Polymerase Chain Reaction
Progesterone / physiology*
RNA, Messenger / genetics
Recombinant Proteins / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinases / metabolism
Transforming Growth Factor beta / genetics*,  metabolism
Grant Support
Reg. No./Substance:
0/Actins; 0/DNA Primers; 0/LEFTY1 protein, human; 0/Left-Right Determination Factors; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Tissue Inhibitor of Metalloproteinases; 0/Transforming Growth Factor beta; 57-83-0/Progesterone; EC 3.4.24.-/Matrix Metalloproteinases

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