The Influence of 17 β-Estradiol on Patterns of Cell Division in the Uterus

Abstract

Uteri from immature (21-day-old) and adult mice show different patterns of cell division in response to a physiological dose of 17 beta-estradiol. In the immature mouse uterus, estradiol increased stromal and epithelial cell proliferation by shortening the cell generation time (Tc). The epithelial Tc was reduced from 100 to 14.5 h; the stromal Tc was reduced to 16 h. In both cell types, the reduction in Tc was primarily due to a reduction of the G1 phase of the cell cycle. In the adult mouse uterus, estradiol stimulated epithelial but not stromal cell proliferation. Here, estradiol reduced the epithelial Tc from 86 to 13 h, mostly by reducing the G1 phase of the cell cycle. Therefore, estrogens stimulate uterine hyperplasia by selectively decreasing the G1 phase of the cell cycle in specific cell populations. At some point during reproductive tract maturation, uterine stromal cells lose their ability to divide in response to estrogen stimulation. A developmental study showed that in the intact mouse, the stromal cell population gradually lost its ability to divide in response to estrogen stimulation during days 22-52 after birth. In prepubertally ovariectomized mice, the stromal cell population showed a very low mitotic response to estrogen stimulation at all ages. Thus, an ovarian mechanism may regulate the change in stromal responsiveness to estrogen stimulation.