Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids

Singer, Christian F.;Marbaix, Etienne;Kokorine, Isabelle;Lemoine, Pascale;Courtoy, Pierre;et.al.
(1997) Proceedings of the National academy of sciences of the United States of America — Vol. 94, n° 19, p. 10341-10345 (1997)

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Authors
  • Singer, Christian F.
    Author
  • Marbaix, EtienneUCLouvain
    Author
  • Kokorine, Isabelle
    Author
  • Lemoine, PascaleUCLouvain
    Author
  • Donnez, JacquesUCLouvain
    Author
  • Eeckhout, YvesUCLouvain
    Author
  • Courtoy, PierreUCLouvain
    Author
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Abstract
In the cycling human endometrium, the expression of interstitial collagenase (MMP-1) and of several related matrix metalloproteinases (MMPs) follows the late-secretory fall in sex steroid plasma concentrations and is thought to be a critical step leading to menstruation. The rapid and extensive lysis of interstitial matrix that precedes menstrual shedding requires a strict control of these proteinases. However, the mechanism by which ovarian steroids regulate endometrial MMPs remains unclear. We report here that, in the absence of ovarian steroids, MMP-1 expression in endometrial fibroblasts is markedly stimulated by medium conditioned by endometrial epithelial cells. This stimulation can be prevented by antibodies directed against interleukin 1alpha (IL-1alpha) but not against several other cytokines. Ovarian steroids inhibit the release of IL-1alpha and repress MMP-1 production by IL-1alpha-stimulated fibroblasts. In short-term cultures of endometrial explants obtained throughout the menstrual cycle, the release of both IL-1alpha and MMP-1 is essentially limited to the perimenstrual phase. We conclude that epithelium-derived IL-1alpha is the key paracrine inducer of MMP-1 in endometrial fibroblasts. However, MMP-1 production in the human endometrium is ultimately blocked by ovarian steroids, which act both upstream and downstream of IL-1alpha, thereby exerting an effective control via a "double-block" mechanism.
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Singer, C. F., Marbaix, E., Kokorine, I., Lemoine, P., Donnez, J., Eeckhout, Y., & Courtoy, P. (1997). Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids. Proceedings of the National academy of sciences of the United States of America, 94(19), 10341-10345. https://doi.org/10.1073/pnas.94.19.10341 (Original work published 1997)