Estrogens and cell death in murine uterine luminal epithelium.
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.
Pollard
J W
JW
Department of Biochemistry, King's College, London, United Kingdom.
Pacey
J
J
Cheng
S V
SV
Jordan
E G
EG
D000818:Animals; D002470:Cell Survival; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D004958:Estradiol / Q000633:toxicity*; D004964:Estriol / Q000633:toxicity*; D005260:Female; D051379:Mice; D010052:Ovariectomy; D012270:Ribosomes / Q000187:drug effects / Q000648:ultrastructure; D014599:Uterus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure
D004958:Estradiol; D004964:Estriol