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Regulation of matrix metalloproteinase-9/gelatinase B expression and activation by ovarian steroids and LEFTY-A/endometrial bleeding-associated factor in the human endometrium.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2005 Feb; Vol. 90 (2), pp. 1001-11. Date of Electronic Publication: 2004 Nov 09. - Publication Year :
- 2005
-
Abstract
- Various matrix metalloproteinases (MMPs) participate in the menstrual breakdown of the human endometrium. MMP-9/gelatinase B is proposed as a major factor because it degrades many extracellular matrix constituents, including in the vasculature. Although globally under ovarian steroids control, endometrial MMP-9 seems expressed differently than other MMPs, and conflicting publications prevent a clear understanding of its regulation. We therefore quantified MMP-9 expression in the cycling human endometrium, defined its localization, and analyzed its regulation by estradiol and progesterone and by LEFTY-A/endometrial bleeding-associated factor in explant cultures. In fresh tissues, a major increase in MMP-9 mRNA expression occurred at menstruation, after a larger increase in LEFTY-A mRNA. MMP-9 was immunodetected in all cell types throughout the cycle, especially in foci of stromal cells during menstruation. MMP-9 synthesis by these cells was confirmed in cultured explants. In proliferative explants, ovarian steroids slightly decreased MMP-9 mRNA. They had no consistent effect on MMP-9 release in culture medium but strongly inhibited proMMP-9 activation. Addition of recombinant LEFTY-A to explants induced MMP-9 in most samples, a response prevented by ovarian steroids. We propose that endometrial MMP-9 activity is overall controlled by the ovarian steroids and locally adjusted through a network of modulators, including LEFTY-A.
- Subjects :
- Base Sequence
Biopsy
Cells, Cultured
DNA Primers
Endometrium drug effects
Endometrium enzymology
Endometrium pathology
Female
Gene Expression Regulation, Enzymologic drug effects
Humans
Left-Right Determination Factors
Menstrual Cycle physiology
Ovary physiology
Polymerase Chain Reaction
Progesterone pharmacology
RNA, Messenger genetics
Endometrium cytology
Matrix Metalloproteinase 9 genetics
Transforming Growth Factor beta genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-972X
- Volume :
- 90
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 15536155
- Full Text :
- https://doi.org/10.1210/jc.2004-1277