HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 71/3/966    most recent biolreprod.104.029512v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Selvaraj, V. Articles by Cooke, P. S. Search for Related Content PubMed PubMed Citation Articles by Selvaraj, V. Articles by Cooke, P. S. Agricola Articles by Selvaraj, V. Articles by Cooke, P. S.

Estrogenicity of the Isoflavone Metabolite Equol on Reproductive and Non-Reproductive Organs in Mice¹

Departments of Veterinary Biosciences,³ Food Science and Human Nutrition,⁴ and Chemistry⁵ and Division of Nutritional Sciences,⁶ University of Illinois at Urbana-Champaign, Urbana, Illinois 61802 National Center for Toxicological Research,⁷ Food and Drug Administration, Jefferson, Arkansas 72079

Equol, a metabolite of the phytoestrogen daidzein, is present at significant levels in some humans who consume soy and in rodents fed soy-based diets. Equol is estrogenic in vitro, but there have been limited studies of its activity in vivo. We evaluated equol effects on reproductive and non-reproductive endpoints in mice. Ovariectomized age-matched (30-day-old) female C57BL/6 mice were fed phytoestrogen-free diets and given a racemic mixture of equol by daily injections (0, 4, 8, 12, or 20 mg [kg body weight]^–1 day^–1) or in the diet (0, 500, or 1000 ppm) for 12 days. Mice were killed, and serum concentrations of total and aglycone equol were measured. Total serum equol concentrations ranged from 1.4 to 7.5 µM with increasing doses of injected equol, but uterine weight increased significantly only at 12 and 20 mg (kg body weight)^–1 day^–1. Dietary equol at 500 or 1000 ppm produced total serum equol concentrations of 5.9 and 8.1 µM, respectively, comparable with those in rodents consuming certain high-soy chows; the proportion of equol present as the free aglycone was much lower with dietary administration than injections, which may be a factor in the greater biological effects induced by injections. Dietary equol did not significantly increase uterine weight. Increasing dietary and injected equol doses caused a dose-dependent increase in vaginal epithelial thickness. Uterine epithelial proliferation was increased by equol injections at 8–20 mg (kg body weight)^–1 day^–1 and 1000 ppm dietary equol. Neither dietary nor injected equol decreased thymic or adipose weights. In conclusion, equol is a weak estrogen with modest effects on endpoints regulated by estrogen receptor when present at serum levels seen in rodents fed soy-based diets, but quantities present in humans may not be sufficient to induce estrogenic effects, although additive effects of equol with other phytoestrogens may occur.

¹ Supported by NIH grants ES011590 (P.S.C.) and CA77355 (W.G.H.). Y.H.J. was supported by an NIEHS Training Program Grant (T32 ES07326).

² Correspondence: William Helferich, Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61802. FAX: 217 244 2455; helferic{at}uiuc.edu. Paul S. Cooke, Department of Veterinary Biosciences, 2001 South Lincoln Avenue, University of Illinois, Urbana, Illinois 61802. FAX: 217 244 1652; p-cooke{at}uiuc.edu

This article has been cited by other articles:

				C. E. Wood, S. E. Appt, T. B. Clarkson, A. A. Franke, C. J. Lees, D. R. Doerge, and J. M. Cline Effects of High-Dose Soy Isoflavones and Equol on Reproductive Tissues in Female Cynomolgus Monkeys Biol Reprod, September 1, 2006; 75(3): 477 - 486. [Abstract] [Full Text] [PDF]

				Y. H. Ju, J. Fultz, K. F. Allred, D. R. Doerge, and W. G. Helferich Effects of dietary daidzein and its metabolite, equol, at physiological concentrations on the growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in ovariectomized athymic mice Carcinogenesis, April 1, 2006; 27(4): 856 - 863. [Abstract] [Full Text] [PDF]

				P. S. Cooke, V. Selvaraj, and S. Yellayi Genistein, Estrogen Receptors, and the Acquired Immune Response J. Nutr., March 1, 2006; 136(3): 704 - 708. [Abstract] [Full Text] [PDF]

				P. Totta, F. Acconcia, F. Virgili, A. Cassidy, P. D. Weinberg, G. Rimbach, and M. Marino Daidzein-Sulfate Metabolites Affect Transcriptional and Antiproliferative Activities of Estrogen Receptor-{beta} in Cultured Human Cancer Cells J. Nutr., November 1, 2005; 135(11): 2687 - 2693. [Abstract] [Full Text] [PDF]

				C. Atkinson, C. L. Frankenfeld, and J. W. Lampe Gut Bacterial Metabolism of the Soy Isoflavone Daidzein: Exploring the Relevance to Human Health Experimental Biology and Medicine, March 1, 2005; 230(3): 155 - 170. [Abstract] [Full Text] [PDF]