Epidermal growth factor and sex steroids dynamically regulate a marker of endometrial receptivity in Ishikawa cells

The factors regulating human endometrial receptivity remain poorly understood. The alpha(v) beta(3) integrin cell adhesion molecule appears to be regulated in the human endometrium, appearing on postovulatory days 5-6, corresponding to the time of initial embryo attachment. This integrin has been extensively studied as a potential marker of endometrial receptivity and is aberrantly expressed in the endometrial epithelium of some infertile women. Ishikawa cells are a well differentiated endometrial adenocarcinoma cell line that maintain functional estrogen and progesterone receptors and are a useful model to study steroid-mediated events in human endometrial epithelium. This cell line expresses most of the normal endometrial epithelial integrins, including the alpha(v) beta(3) vitronectin receptor. The regulation of this integrin was studied with fluorescence immunocytochemistry, now cytometry, and Northern blot analysis. Estrogen with or without progesterone treatment down-regulates alpha(v) beta(3) in this cell line. Several growth factors, including epidermal growth factor and the closely related transforming growth factor-alpha significantly increase the expression of this integrin. We conclude that endometrial differentiation is influenced by both steroid hormones and growth factors. The alpha(v) beta(3), integrin appears to be an excellent marker to study the molecular events leading to the establishment of uterine receptivity and successful implantation.