Estrogen receptors and the estrone hypothesis in relation to endometrial and breast cancer

Pentti K. Siiteri, Barry E. Schwarz, Paul C. MacDonald

Research output: Contribution to journalArticle

101 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)228-238
Number of pages11
JournalGynecologic Oncology
Volume2
Issue number2-3
DOIs
StatePublished - 1974

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Estrone
Endometrial Neoplasms
Estrogen Receptors
Breast Neoplasms
Cytoplasmic and Nuclear Receptors
Estriol
Estrogens
Neoplasms
Ultracentrifugation
Endometrium
Sucrose
Estradiol
Pregnancy
Incidence
Population

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Estrogen receptors and the estrone hypothesis in relation to endometrial and breast cancer. / Siiteri, Pentti K.; Schwarz, Barry E.; MacDonald, Paul C.

In: Gynecologic Oncology, Vol. 2, No. 2-3, 1974, p. 228-238.

Research output: Contribution to journalArticle

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