Ovarian steroid and cytokine modulation of human endometrial angiogenesis

A key mechanism underlying the cyclical growth of the endometrium is its ab ility to regenerate a vascular capillary network. In normal cycling human e ndometrium, angiogenesis is influenced by both endocrine and paracrine fact ors. Hormonal manipulation of the endometrium, such as that occurring durin g the use of steroidal contraception, appears to result in capillary prolif eration and fragility. As a consequence of these vascular changes, contrace ptive users may be predisposed to unpredictable uterine bleeding, which is responsible for the high frequency of contraceptive discontinuation. In thi s paper we address mechanisms responsible for vascular endothelial cell pro liferation in normal and contraceptive steroid-exposed endometria, We propo se that regulation of endometrial angiogenesis is mediated indirectly, via steroid and cytokine actions on vascular endothelial growth factor (VEGF), and we present data indicating that VEGF expression in normal endometrial s tromal cells is increased by oestrogens and progestins, Three proinflammato ry cytokines with angiogenic effects in other systems (i.e. interleukin-1 b eta, tumour necrosis factor-alpha and interferon-gamma) do not appear to up -regulate VEGF expression in normal endometrial stromal cells. Well-charact erized in-vitro models in conjunction with immunohistochemistry provide use ful experimental systems to study endometrial neovascularization under phys iological conditions and in those potentially perturbed via the use of cont raceptive steroids.