Regulation of Matrix Metalloproteinase-9/Gelatinase B Expression and Activation by Ovarian Steroids and LEFTY-A/Endometrial Bleeding-Associated Factor in the Human Endometrium

Patricia B. Cornet, Christine Galant, Yves Eeckhout, Pierre J. Courtoy, Étienne Marbaix, Patrick Henriet
In: The Journal of Clinical Endocrinology & Metabolism · 2005 · vol. 90(2) , pp. 1001–1011 · doi:10.1210/jc.2004-1277 · PMID:15536155 · W2059912978
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This study quantified human endometrial MMP-9 expression and found its activity is controlled by ovarian steroids and modulated by LEFTY-A, with increased MMP-9 mRNA coinciding with menstruation.

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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.

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