The matrix metalloproteinase-1 (MMP-1) expression in the human endometrium is inversely regulated by interleukin-1 alpha and sex steroids.
OBJECTIVE
To investigate the regulation of perimenstrual MMP-1 expression in human endometrium.


METHODS
In vitro study utilizing epithelial-stromal co-cultures.


METHODS
Cell Biology Unit, International Institute of Cellular and Molecular Pathology, and Departments of Pathology and Gynecology, Saint-Luc University Clinics, Louvain University Medical School, Brussels, Belgium.


METHODS
Contact-dependent and contact-independent co-cultures were established and resulting MMP-1 gene and protein expression was analyzed by RNase protection assays and soluble-collagen assays.


RESULTS
MMP-1 expression in endometrial fibroblasts is markedly stimulated by epithelial cell-conditioned medium. This stimulation can be prevented by antibodies directed against interleukin 1 alpha (IL-1 alpha). Ovarian steroids inhibit MMP-1 production by IL-1 alpha-stimulated fibroblasts in vitro.


CONCLUSIONS
Taken together, our results suggest that epithelium-derived IL-1 alpha is the most important paracrine induced of MMP-1 in endometrial fibroblasts. However, IL-1 alpha-stimulated MMP-1 production in the human endometrium is effectively blocked by ovarian steroids. We believe that this mechanism responsible for the MMP-1 repression that occurs when systemic sex steroid concentrations are high and the MMP-1 production and activity during the perimenstrual phase when estrogen and progesterone concentrations are low.
Singer
C F
CF
International Institute of Cellular and Molecular Pathology, Université Catholique de Louvain, Austria.
Marbaix
E
E
Kokorine
I
I
Lemoine
P
P
Donnez
J
J
Eeckhout
Y
Y
Courtoy
P J
PJ
D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis*; D008598:Menstruation
D017077:Culture Media, Conditioned; D012739:Gonadal Steroid Hormones; D007375:Interleukin-1; D020781:Matrix Metalloproteinase 1