TY - JOUR
T1 - Estrogenicity of the isoflavone metabolite equol on reproductive and non-reproductive organs in mice
AU - Selvaraj, Vimal
AU - Zakroczymski, Melissa A.
AU - Naaz, Afia
AU - Mukai, Motoko
AU - Ju, Young H.
AU - Doerge, Daniel R.
AU - Katzenellenbogen, John A.
AU - Helferich, William G.
AU - Cooke, Paul S.
PY - 2004/9
Y1 - 2004/9
N2 - 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 a 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.
AB - 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 a 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.
KW - Female reproductive tract
KW - Steroid hormone receptors
KW - Uterus
KW - Vagina
UR - http://www.scopus.com/inward/record.url?scp=4243079870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4243079870&partnerID=8YFLogxK
U2 - 10.1095/biolreprod.104.029512
DO - 10.1095/biolreprod.104.029512
M3 - Article
C2 - 15151933
AN - SCOPUS:4243079870
SN - 0006-3363
VL - 71
SP - 966
EP - 972
JO - Biology of reproduction
JF - Biology of reproduction
IS - 3
ER -