EPIDERMAL GROWTH-FACTOR AND SEX STEROIDS DYNAMICALLY REGULATE A MARKER OF ENDOMETRIAL RECEPTIVITY IN ISHIKAWA CELLS

The factors regulating human endometrial receptivity remain poorly und erstood. The alpha(v) beta(3) integrin cell adhesion molecule appears to be regulated in the human endometrium, appearing on postovulatory d ays 5-6, corresponding to the time of initial embryo attachment. This integrin has been extensively studied as a potential marker of endomet rial receptivity and is aberrantly expressed in the endometrial epithe lium of some infertile women. Ishikawa cells are a well differentiated endometrial adenocarcinoma cell line that maintain functional estroge n and progesterone receptors and are a useful model to study steroid-m ediated events in human endometrial epithelium. This cell line express es 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 treatme nt down-regulates alpha(v) beta(3) in this cell line. Several growth f actors, including epidermal growth factor and the closely related tran sforming growth factor-alpha significantly increase the expression of this integrin. We conclude that endometrial differentiation is influen ced by both steroid hormones and growth factors. The alpha(v) beta(3), integrin appears to be an excellent marker to study the molecular eve nts leading to the establishment of uterine receptivity and successful implantation.