1,3,5[10]-ESTRATRIENE-3,16ALPHA-DIOL-17-ONE

Description

The naturally-occurring estrogens are estrone (E₁, ), estradiol (E₂, ), and estriol (E₃, ). 16α-hydroxy Estrone (16α-OHE₁) is a hydroxylated metabolite of E₁ as well as an interconversion product with E₂. E₁ is 16α-hydroxylated by cytochrome P450 (CYP) isoforms, including CYP1A1, CYP3A5, CYP3A4, and CYP3A7, with CYP3A5 being breast-specific. 16α-OHE₁ is sulphatized or glucuronidated before excretion. It is increased in rheumatoid arthritis and decreased by physical activity. Unlike the parent estrogens and other hydroxylated metabolites of E₁, 16α-OHE₁ binds covalently and persistently activates estrogen receptors. In addition, this metabolite increases cell proliferation and does not suppress TNF-α secretion, whereas other estrogen metabolites are not pro-proliferative and have marked effects on TNF-α secretion. The levels of 16α-OHE₁ are increased in some forms of hormone therapy. Because hormone therapy increases breast cancer risk, 16α-OHE₁ has been implicated as a risk factor for breast cancer, although supportive data remains elusive.

Chemical Properties

Pale Pink Solid

Uses

16α-Hydroxy Estrone (Estriol EP Impurity H) is a major metabolite of Estradiol.

Definition

ChEBI: The 16alpha-hydroxy derivative of estrone; a minor estrogen metabolite.

IC 50

Human Endogenous Metabolite

References

[1] MAURIZIO CUTOLO  Rainer H S  Alberto Sulli. Estrogen metabolism and autoimmunity[J]. Autoimmunity reviews, 2012, 11 6: Pages A460-A464. DOI: 10.1016/j.autrev.2011.11.014
[2] CHARLES E MATTHEWS. Association between physical activity and urinary estrogens and estrogen metabolites in premenopausal women.[J]. Journal of Clinical Endocrinology & Metabolism, 2012, 97 10: 3724-3733. DOI: 10.1210/jc.2012-1732
[3] NADIA OBI. Estrogen metabolite ratio: Is the 2-hydroxyestrone to 16α-hydroxyestrone ratio predictive for breast cancer[J]. International Journal of Women’s Health, 2011, 3: 37-51. DOI: 10.2147/ijwh.s7595
[4] G E SWANECK  J F. Covalent binding of the endogenous estrogen 16 alpha-hydroxyestrone to estradiol receptor in human breast cancer cells: characterization and intranuclear localization.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1988, 85 21: 7831-7835. DOI: 10.1073/pnas.85.21.7831
[5] RACHEL H MACKEY. Hormone therapy, estrogen metabolism, and risk of breast cancer in the Women’s Health Initiative Hormone Therapy Trial.[J]. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2012: 2022-2032. DOI: 10.1158/1055-9965.epi-12-0759
[6] M N OKOBIA  C H B. Estrogen metabolism and breast cancer risk–a review.[J]. African journal of reproductive health, 2006, 10 1: 13-25.