Paracrine regulation of matrix metalloproteinase expression in the normal human endometrium.
Endometrial expression of matrix metalloproteinase (MMP)-3, MMP-7 and MMP-11 occurs during menstrual breakdown and subsequent estrogen-mediated growth, but not during the secretory phase. These enzymes are suppressed by progesterone treatment. Paracrine factors, including transforming growth factor-beta (TGF-beta) and retinoic acid, are also critical for MMP regulation in the endometrium. In contrast, inflammatory cytokines such as interleukin-1alpha may block or interfere with steroid-mediated MMP regulation at ectopic sites of growth. Using in vitro models, our laboratory has investigated the complex interactions between progesterone and locally produced cytokines that may affect MMP expression during the development of endometriosis. Our results indicate that targeting the regulation of MMPs may represent an appropriate therapeutic strategy for the treatment of endometriosis. Copyrightz1999S. KargerAG,Basel
Osteen
K G
KG
Women's Reproductive Health Research Center, Vanderbilt University School of Medicine, Nashville, Tenn. 37232, USA. kevin.osteen@mcmail.vanderbilt.edu
Keller
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NR
Feltus
F A
FA
Melner
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MH
D000328:Adult; D015153:Blotting, Western; D002855:Chromatography, Thin Layer; D004715:Endometriosis / Q000201:enzymology / Q000503:physiopathology* / Q000628:therapy; D004717:Endometrium / Q000201:enzymology / Q000502:physiology*; D004958:Estradiol / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D053507:Matrix Metalloproteinase 11; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008597:Menstrual Cycle / Q000502:physiology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014212:Tretinoin / Q000502:physiology
D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D011374:Progesterone; D004958:Estradiol; D014212:Tretinoin; D053507:Matrix Metalloproteinase 11; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7