title: 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 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 1,000 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 microM 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 1,000 ppm produced total serum equol concentrations of 5.9 and 8.1 microM, 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 1,000 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 alpha 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.
authors.affiliation: Department of Veterinary Biosciences, University of Illinois at Urbana-Champaign, Urbana, Illinois 61802, USA.
authors.forename: Vimal
authors.initials: V
authors.lastname: Selvaraj
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Zakroczymski
authors.forename: Afia
authors.initials: A
authors.lastname: Naaz
authors.forename: Motoko
authors.initials: M
authors.lastname: Mukai
authors.forename: Young H
authors.initials: YH
authors.lastname: Ju
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
authors.forename: Paul S
authors.initials: PS
authors.lastname: Cooke
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D060754:Equol; D005260:Female; D007529:Isoflavones / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D048789:Phytoestrogens / Q000097:blood / Q000494:pharmacology*; D045730:Soy Foods; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects*; D014621:Vagina / Q000033:anatomy & histology / Q000187:drug effects*
chemical_list: C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D007529:Isoflavones; D048789:Phytoestrogens; D060754:Equol