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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.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 Nov 08; Vol. 277 (45), pp. 42496-504. Date of Electronic Publication: 2002 Sep 04. - Publication Year :
- 2002
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Abstract
- 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.
- Subjects :
- Actins metabolism
Base Sequence
DNA Primers
Endometrium drug effects
Female
Humans
Left-Right Determination Factors
Organ Culture Techniques
Polymerase Chain Reaction
RNA, Messenger genetics
Recombinant Proteins pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinases metabolism
Transforming Growth Factor beta metabolism
Endometrium physiology
Gene Expression Regulation drug effects
Matrix Metalloproteinases metabolism
Menstrual Cycle physiology
Progesterone physiology
Transforming Growth Factor beta genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 45
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12215426
- Full Text :
- https://doi.org/10.1074/jbc.M201793200