Singer, Christian F.
Marbaix, Etienne
[UCL]
Kokorine, Isabelle
Lemoine, Pascale
[UCL]
Donnez, Jacques
[UCL]
Eeckhout, Yves
[UCL]
Courtoy, Pierre J.
[UCL]
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.
Bibliographic reference |
Singer, Christian F. ; Marbaix, Etienne ; Kokorine, Isabelle ; Lemoine, Pascale ; Donnez, Jacques ; et. al. Paracrine stimulation of interstitial collagenase (MMP-1) in the human endometrium by interleukin 1alpha and its dual block by ovarian steroids. In: Proceedings of the National academy of sciences of the United States of America, Vol. 94, no. 19, p. 10341-10345 (1997) |
Permanent URL |
http://hdl.handle.net/2078.1/25253 |