Journal Article

Isoflavones modulate the glucuronidation of estradiol in human liver microsomes

Erika Pfeiffer, Christian R. Treiling, Simone I. Hoehle and Manfred Metzler

in Carcinogenesis

Volume 26, issue 12, pages 2172-2178
Published in print December 2005 | ISSN: 0143-3334
Published online July 2005 | e-ISSN: 1460-2180 | DOI:
Isoflavones modulate the glucuronidation of estradiol in human liver microsomes

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  • Clinical Cytogenetics and Molecular Genetics


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Soy food has been associated with a reduced incidence of hormonal cancer in Asian countries, and the soy isoflavones daidzein and genistein are believed to protect against tumors induced by the endogenous hormone 17β-estradiol (E2). In the present study, we have examined if daidzein and genistein as well as several structurally related isoflavones are able to modulate the in vitro glucuronidation of E2 in human hepatic microsomes. It is known that different isoforms of UDP-glucuronosyltransferase (UGT) are involved in E2 glucuronidation: UGT1A1 leads exclusively to the 3-glucuronide and is stimulated by E2 via homotropic kinetics, whereas UGT2B7 gives rise to the 17-glucuronide of E2 following Michaelis–Menten kinetics. In our study, daidzein markedly stimulated the 3-glucuronidation, thereby enhancing the metabolic clearance of E2. In contrast, genistein inhibited the 3-glucuronidation. The 17-glucuronidation of E2 was not affected by either compound. Formononetin and the daidzein metabolites equol, 3′-hydroxy-daidzein, 6-hydroxy-daidzein and glycitein behaved similar to daidzein, whereas biochanin A resembled genistein. The effect of daidzein on the 3-glucuronidation of E2 in human hepatic microsomes was also obtained with human recombinant UGT1A1. Since the only other compound known to stimulate E2 glucuronidation via allosteric kinetics is 17α-ethynylestradiol, our study is the first report of the heterotropic stimulation of a UGT by a non-steroidal and naturally occurring compound. An enhanced rate of glucuronidation of E2 by daidzein and its metabolites may contribute to the putative protection of soy against hormonal cancer.

Keywords: E2, 17β-estradiol; E2-3-G, 17β-estradiol-3-glucuronide; E2-17-G, 17β-estradiol-17-glucuronide; HLM, human liver microsomes; HPLC, high performance liquid chromatography; UGT, uridine diphosphoglucuronosyltransferase

Journal Article.  5235 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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