Female Reproductive Tract

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

Abstract
Equol, a metabolite of the phytoestrogen daidzein, is present at significant levels in some humans consuming 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 BW/day) or in the diet (0, 500 or1000 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 - 7.5 µM with increasing doses of injected equol, but uterine weight increased significantly only at 12 and 20 mg/kg BW/day. Dietary equol at 500 or 1000 ppm produced total serum equol concentrations of 5.9 and 8.1 µM, respectively, comparable to those in rodents consuming certain high-soy chows; the proportion of equol present as the free aglycone was much lower with dietary adminstration 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 BW/day 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, though additive effects of equol with other phytoestrogens may occur.

Key words: Female Reproductive Tract • Steroid hormone receptors • Uterus • Vagina

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]