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

Abstract

Remodelling of endometrial tissues is fundamental to the cyclical changes that occur during the menstrual cycle, implantation and, in the absence of pregnancy, 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 glandular and stromal cells. MMP-9 protein is present throughout the cycle with highest expression, as determined by semi-quantitative analysis of specific MMP-9 immunoreactivity, in glandular cells during the mid secretory phase. A similar distribution was observed in first trimester decidua. In women with a levonorgestrel intrauterine system (LNG-IUS), which delivers high local concentrations of progestagen to the uterine cavity. MMP-9 is highly expressed in both endometrial glandular and stromal cells, and in the vasculature (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 the menstrual cycle and in the aetiology of the morphological changes and breakthrough bleeding associated with long-term progestagen administration via a LNG-IUS.