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A Okada, Y Ohta, SL Brody, and T Iguchi

Expression of transcription factors binding to the activating protein-1 (AP-1) site is induced by estrogens in association with epithelial proliferation in the uterus, but, in the oviduct, the relationship between cell proliferation and differentiation and AP-1 transcription factors is not well understood. In the developing rat oviduct, we found that proliferation and differentiation of epithelial cells were region-dependently regulated by 17beta-estradiol (E2). To determine the role of AP-1 transcription factors in the development of rat oviduct, we performed immunohistochemistry for epithelial c-jun and c-fos proteins in E2-untreated and -treated newborn rats. E2 increased the expression of c-jun and c-fos during proliferation of undifferentiated epithelial cells, but diminished both proteins during accelerated differentiation of ciliated epithelial cells. A pure estrogen receptor (ER) antagonist, ICI 182,780, inhibited changes in their expression during both cell proliferation and differentiation. Importantly, no reduction of c-jun was noted in the epithelial cells of the foxj1-deficient oviduct, which lacks cilia development. This study shows that c-jun and c-fos are regulated during epithelial cell proliferation and differentiation in a region-specific manner. This provides critical information for understanding the molecular and cellular mechanisms of the development of the neonatal oviduct.