Regulation of matrix metalloproteinase-9 in endometrium during the menstrual cycle and following administration of intrauterine levonorgestrel

Remodelling of endometrial tissues is fundamental to the cyclical changes t hat occur during the menstrual cycle, implantation and, in the absence of p regnancy, at menstruation, The enzyme matrix metalloproteinase-9 (MMP-9) is recognized as important in these processes but its regulation is not well defined. These studies have demonstrated that MMP-9 activity is present in the endometrium and exhibits cyclical changes in its distribution in the gl andular and stromal cells, MMP-9 protein is present throughout the cycle wi th highest expression, as determined by semiquantitative analysis of specif ic MMP-9 immunoreactivity, in glandular cells during the mid secretory phas e, A similar distribution was observed in first trimester decidua, In women with a levonorgestrel intrauterine system (LNG-IUS), which delivers high l ocal concentrations of progestagen to the uterine cavity, MMP-9 is highly e xpressed in both endometrial glandular and stromal cells, and in the vascul ature (in endothelial and perivascular cells). It can be concluded that MMP -9 is stimulated directly or indirectly by progesterone, Furthermore, MMP-9 may play a role in the remodelling of the endometrium that occurs during t he menstrual cycle and in the aetiology of the morphological changes and br eakthrough bleeding associated with long-term progestagen administration vi a a LNG-IUS.