Steroids and cytokines in endometrial angiogenesis

Angiogenesis, the formation of new blood vessels from pre-existing ones, occurs physiologically in the endometrium and pathologically e.g. during tumour growth. Sex-steroid hormones affect angiogenesis in the endometrium during the menstrual cycle and might be implicated in cancer angiogenesis. Little information is presently available regarding the exact mechanisms by which these steroids exert their function on the process of both physiological and pathological angiogenesis. In this overview a survey is given of factors important for angiogenesis and of the effects of steroids on the expression of these factors. We have focused on endometrial angiogenesis, because the endometrium is unique in its cyclic growth pattern for which angiogenesis is indispensable. Stimulators and inhibitors of endometrial angiogenesis, that have been found (or suggested) to respond to ovarian steroids, are discussed These factors include vascular endothelial growth factor (VEGF), fibroblast growth factors (FGFs), tumour necrosis factor a (TNF-alpha), erythropoietin (Epo) and trombospondin-1 (TSP-1). Also, the influence of steroids on the expression of matrixdegrading proteases, in particular the plasminogen activator/plasmin system and matrixdegrading metalloproteinases (MMPs) are reviewed, because these proteases play an important role in the migration and invasion of endothelial cells during the process of angiogenesis. An insight into the effects of steroids on endometrial angiogenesis may be helpful to understand and anticipate the potential stimulatory and inhibitory effect of various steroids on angiogenesis in other tissues, in particular tumours.