Estrogens and cell death in murine uterine luminal epithelium

Abstract

The luminal epithelium of adult ovariectomized mice responds to estradiol-17 beta with a synchronised wave of DNA synthesis and mitosis. Estriol, however, although producing a similar DNA-synthetic and mitotic response fails to cause an increase in cell number owing to a wave of cell death occurring at mitosis. In the present study it was shown that cells died by two different routes. The majority died by apoptosis but, unusually, a minority also died by necrosis. In the apoptotic cells the cytoplasm became dense, the endoplasmic reticulum and nuclear cisternae dilated; chromatin became marginated the nucleus shrank and became deeply infolded and contorted. Apoptosis, however, was uncharacteristic in that the nucleus failed to fragment, form caps or show disruption before the cells died by membrane rupture. Furthermore, the cells were frequently lost in sheets from the epithelium into the lumen. Part of the biochemical explanation for this onset of cell death comes from the accelerated loss from the tissue of estriol when compared to estradiol-17 beta. This resulted in a decline in protein and rRNA biosynthesis and a failure to complete ribosomal maturation. Evidence in favour of this explanation came from experiments that showed a return to the estradiol-17 beta level of response and an inhibition of cell death when the occupancy of the estriol receptor was maintained.

Apoptosis and 1-methyl-2-nitroimidazole toxicity in CHO cells

“…These results were consistent with previous experiments after a 1-h acute hypoxic exposure to 40 mm INO,, which revealed extensive membrane blebbing, nuclear condensation and organelle compaction, as assessed by transmission and scanning electron microscopy (Brezden et al, 1994 (Fernandes and Cotter, 1994 (Figure 3) and apoptotic morphology ( Figure 4B) (Figure 3) is consistent with the requirement of cells initiating the apoptotic cell death programme in an attempt to re-enter mitosis (Pollard et al, 1987;Columbel et al, 1992). In contrast, cell cycle analysis of cells treated with 40 mM INO, provides evidence that cells attempt to activate apoptosis as observed by the large sub-GI population at day 1 after acute exposure ( Figure SB).…”

Hormonal regulation of physiological cell turnover and apoptosis

“…2) (Martin and Finn 1968;Sandow et al 1979). Estrogen promotes epithelial cell proliferation in the uterine endometrium (Pollard et al 1987). In the luteal phase of the ovarian cycle, progesterone secretion is predominant, promoting epithelial cell differentiation and initiation of the secretory phase of the endometrial cycle (Dallenbach-Hellweg 1988).…”

“…More detailed studies repeatedly have confirmed the key role of the sex steroids in endometrial cell turnover. In the mouse uterus, 17β-estradiol treatment results in epithelial proliferation, while an inactive estrogen, estriol, causes epithelial cell loss via apoptosis, which can be prevented by progesterone and estrogen (Pollard et al 1987). Progesterone has been reported to block 17β-estradiol-induced cell proliferation of epithelial cells in mouse uterine endometrium (Terada et al 1989).…”

Distinct Signaling Pathways Mediate Stimulation of Cell Cycle Progression and Prevention of Apoptotic Cell Death by Estrogen in Rat Pituitary Tumor PR1 Cells

“…Estrogens, in fact, control the function of several genes and proteins directly involved in cell cycle regulation, including cyclins, proto-oncogenes, and negative cell cycle regulators (Altucci et al, 1996;Dinda et al, 1997), although they are well known modulators of cell life and death in different cell types, including uterine epithelia (Pollard et al, 1987), breast cancer cells (Kyprianou et al, 1991), and neurons (Singer et al, 1996;Sawada et al, 2000). The cellular mechanism(s) mediating estrogen prevention of programmed cell death has not been clarified yet.…”