The purpose of this project is to understand better the development of the endometrium and oocyte in women and to investigate the role of gonadal steroids in these processes. The process of uterine remodeling that is so remarkable in the mammalian uterus is achieved through coordinated proliferation, differentiation and cell death. While the gonadal steroids estradiol and progesterone appear to be required for these organ-specific processes, the mechanism(s) by which these processes are regulated remain unclear. Recent studies have been directed to characterization of growth factors responsible for paracrine coordination of stromal and epithelial growth. Preliminary data suggest that scatter factor and its receptor, MET, are present in the endometrium of normally cycling women. This suggests that this growth factor-receptor dyad may play a role in epithelial differentiation. Molecular characterization of the promoter region of the MET gene revealed that hepatocyte growth factor and phorbol esters, but not steroid hormones, enhance transcription from the MET promoter in transfected Ishikawa cells. Other efforts characterized the biologic action of the antiprogestin CDB 2914, showing it to cause dose-dependent endometrial shedding when given to normally cycling women in the luteal phase.
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