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BOR - Papers in Press, published online ahead of print May 28, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.015933
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BIOLOGY OF REPRODUCTION 69, 976–984 (2003)
DOI: 10.1095/biolreprod.103.015933
© 2003 by the Society for the Study of Reproduction, Inc.


Female Reproductive Tract

Expression Pattern of Metalloproteinases and Tissue Inhibitors of Matrix-Metalloproteinases in Cycling Human Endometrium1

Frédéric Goffin3,4, Carine Munaut3, Francis Frankenne3, Sophie Perrier d'Hauterive4, Aude Béliard3, Viviana Fridman5, Patricia Nervo4, Alain Colige6, and Jean-Michel Foidart2,3,4

Departments of Tumor and Development Biology,3 Obstetrics and Gynecology,4 Pathology,5 Connective Tissue Biology,6 Faculty of Medicine, University of Liège, 4000 Liège, Belgium

The cyclic growth, differentiation, and cell death of endometrium represents the most dynamic example of steroid-driven tissue turnover in human adults. Key effectors in these processes—matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs)—are regulated by ovarian steroids and, locally, by cytokines. We used reverse transcription-polymerase chain reaction to evaluate the expression of both transcriptionally regulated molecules such as estrogen receptor-{alpha}, progesterone receptor, and prolactin and a large array of MMPs and TIMPs (MMP-1, -2, -3, -7, -8, -9, -11, -12, -19, -26, MT1-MMP, MT2-MMP, MT3-MMP, TIMP-1, -2, -3). Altogether, three distinct patterns of MMP and two patterns of TIMP expression were detected in cycling endometrium: 1) MMPs restricted to the menstrual period (MMPs-1, -3, -8, -9, -12); 2) MMPs and TIMPs expressed throughout the cycle (MMP-2, MT1-MMP, MT2-MMP, MMP-19, TIMP-1, and TIMP-2); 3) MMPs predominantly expressed during the proliferative phase (MMP-7, MMP-11, MMP-26, and MT3-MMP); and 4) TIMP-3, which, contrary to the other TIMPs, shows significant modulations, with maximum expression during the late secretory and menstrual phases. These specific patterns of MMP expression associated with each phase of the cycle may point to specific roles in the processes of menstruation, housekeeping activities, angiogenesis, tissue growth, and extracellular matrix remodeling.

1 This work was supported by grants from the Communauté française de Belgique (Actions de Recherches Concertées), the Commission of European Communities, the Fonds de la Recherche Scientifique Médicale, the Fonds National de la Recherche Scientifique (FNRS, Belgium), the Fédération Belge Contre le Cancer, C.G.R.I.-F.N.R.S.-INSERM 2001 Coopération, the Fonds spéciaux de la Recherche (University of Liège), the Centre Anticancéreux près l'Université de Liège, FB Assurances, the Fondation Léon Frédéricq (University of Liège), Région Wallonne D.G.T.R.E., and the Fonds d'Investissements de la Recherche Scientifique (CHU, Liège, Belgium). F.G. and S.P. are Research Assistants, and C.M. is a Research Associate of Fonds National de la Recherche Scientifique (FNRS, Belgium). F.G. and C.M. contributed equally to this work.

2 Correspondence: Jean-Michel Foidart, Laboratory of Tumoral and Developmental Biology, Tour de Pathologie B-23, CHU Sart-Tilman, 4000 Liège, Belgium. FAX: 32 4 366 29 36; jmfoidart{at}ulg.ac.be




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