Estrogen regulates DNA synthesis in human gingival epithelial cells displaying strong estrogen receptor β immunoreactivity

Background and Objective: Estrogen acts via estrogen receptor (ER) alpha and beta. The expression pattern of ERs and their importance in gingival tissues are not fully understood. In this study, we investigate gingival ER expression and effects of estrogen on gingival epithelial cell proliferation. Material and Methods: Gingival biopsies were obtained from both healthy and diseased sites in three male and three female subjects. Expression of ER alpha and beta was determined by immunohistochemistry. Effects of 17 beta-estradiol (E(2)) on cell proliferation, monitored by measuring DNA synthesis, were studied in cultured human gingival epithelial HGEPp. 05 cells. Results: Estrogen receptor beta, but not ER alpha, immunoreactivity was demonstrated in nuclei of epithelial cells in all layers of the gingival epithelium, but also in cells of the lamina propria. No differences were observed between male and female subjects. The same pattern, i.e. high ER beta expression but no ER alpha expression, was observed in both healthy and diseased sites within each individual. No differences in the intensity of the ER beta immunoreactive signal and the number of ER beta-positive nuclei were observed between healthy and diseased gingiva. Treatment with a physiological concentration of E(2) (10 nM) had no effect on DNA synthesis in ER beta- and ER alpha-expressing HGEPp. 05 cells. In contrast, E(2) at high concentrations (500 nM and 10 mu M) reduced DNA synthesis by 60-70%. Conclusion: Human gingival epithelial cells display strong ER beta but low ER alpha immunoreactivity both in vivo and in culture. Estrogen attenuates gingival epithelial cell DNA synthesis at high but not low concentrations, suggesting a concentration- dependent mechanism.