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Abstract
Estrogen binding to normal and abnormal human endometrial cytoplasmic and nuclear
receptors has been demonstrated by sucrose density-gradient ultracentrifugation. Estrone
binds to cytoplasmic receptor, and the resulting complex is transferred into the nucleus,
suggesting that estrone is an active estrogen in human endometrium. Estriol at equimolar
concentrations effectively competes with estrone for binding to immature rat uterine
cytoplasmic receptor, whereas much higher concentrations are required for effective
competition with estradiol. Together with our extensive studies demonstrating the
exclusive production of estrone by anovulatory subjects having a high risk for development
of endometrial or breast cancer, these results have led to the formulation of the
“estrone hypothesis.” This hypothesis suggests that unopposed exposure of target tissues
to estrone may be a causal factor in the development of cancer. The postulated “protective
effect” of estriol in low cancer incidence populations (Japanese) and the beneficial
effects of pregnancy on cancer risk can be explained on the basis of these findings.
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Article info
Publication history
Received:
March 11,
1974
Identification
Copyright
© 1974 Published by Elsevier Inc.
