Evidence for actions of estrone distinct from those of estradiol

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ID: 314197
2026
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Abstract
Abstract Context Recent studies challenge the traditional view that estrone (E1) must be converted to estradiol (E2) to be biologically active. The prior view was based on several findings: E2 binds to ERα and ERβ, and their nuclear coactivators, with 4 to 25 times greater affinity than E1. 17β-hydroxysteroid dehydrogenases can efficiently convert E1 to E2 in vivo. Observations from cell culture, animal models, and clinical studies have supported the idea that E1’s biological effects depend on its conversion to E2. Evidence Acquisition A systematic search was conducted using PubMed, Ovid Medline, Embase, Web of Science and bibliographies of manuscripts to obtain pertinent data. Evidence synthesis In postmenopausal women, plasma levels of E1 are 4-fold higher than those of E2, and the E1 production through peripheral aromatization is 8-fold higher. Recent research has shown that E1 has distinct effects on brain function, gene expression, breast tissue inflammation, immune modulation, epithelial to mesenchymal cell transformation (EMT), stem cells, and vascular endothelial cells. The specific recruitment of coactivators to enhancer complexes during nuclear transcription may explain these unique actions of E1. Collectively, these findings provide evidence that E1 can act independently of conversion to E2. Extensive study is now required regarding clinical implications for the selection of type of estrogen therapy after menopause, especially regarding cognitive function, mood disorders, and effects on breast inflammation ‘ Conclusion Current evidence indicates that E1 is a biologically significant estrogen in its own right. Further preclinical and clinical studies are needed to clarify E1’s unique effects.
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Authors Richard J. Santen, Anne Gompel, Karen O Klein, Mary Ann Lumsden, JoAnn V Pinkerton, Cynthia A. Stuenkel, Wei Yue
Journal the journal of clinical endocrinology & metabolism
Year 2026
DOI
10.1210/clinem/dgag213
URL
https://doi.org/10.1210/clinem/dgag213
Keywords Keywords not found

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