[Collagenase and Related Matrix Metalloproteinases - a Prominent Role in the Initiation of Menstruation]

The human endometrium shows striking structural changes during the menstrual cycle. If no pregnancy develops, the fall of plasma progesterone and estradiol induces extracellular matrix degradation leading to haemorrhagia and mucosal shedding, i. e. menstruation. The mechanisms of endome trial tissue breakdown remain obscure. A major role of lysosomal hydrolases is not supported by biochemical evidence, whereas recent studies by several laboratories including our own suggest that interstitial collagenase and related matrix metalloproteinases (MMPs) are involved. We have demonstrated that human endometrium in tissue culture can produce interstitial collagenase and gelatinases A and B. Both the expression and the activation of these MMPs were inhibited by physiological concentrations of progesterone and estradiol. Moreover, in fresh human endometrial tissue, expression of mRNA, protein and activity of interstitial collagenase, as well as of mRNA of several other MMPs is limited to the perimenstrual period. In such tissues, immunolocalisation and in situ hybridization show that the expression is focal. The tight hormonal control as well as the restricted temporal and spatial expression of MMPs in human endometrium all point to a pivotal role of interstitial collagenase and other MMPs in the initiation of menstruation