Estrogenic activity of flavonoids in mice. The importance of estrogen receptor distribution, metabolism and bioavailability

The in vivo estrogenic potential of the flavonoids apigenin, kaempferol, ge nistein and equol was investigated in immature female mice. Genistein and e quol, administered by gavage for 4 consecutive days [post-natal day (PND) 1 7-20, 100 mg/kg body weight], was found to significantly increase uterine w eights and the overall uterine concentration of estrogen receptor alpha (ER alpha). In kaempferol- and equol-exposed mice the cytosolic ER alpha conce ntration was significantly increased as compared to the solvent control, wh ich is speculated to result in an increased sensitivity of the uterus to su bsequently encountered estrogens. Oral administration of equol, genistein, biochanin A and daidzein to 6-week-old female mice revealed a great variati on in their systemic bioavailability. The urinary recovery of equol was thu s over 90% of a single gavage administered dose, whereas the urinary recove ries of biochanin A, genistein and daidzein were 16, 11 and 3%, respectivel y. Most of the metabolites were either hydroxylated or dehydrogenated forms of the parent compounds. The in vitro estrogenic potency of some of the me tabolites was greater than that of the parent compounds, whereas others wer e of similar or lower potency. Bioavailability, metabolism, the ability to alter ER alpha distribution in the uterus and the estrogenic potential of p arent compound and metabolites may thus contribute to the differences in in vivo estrogenicity of dietary flavonoids. (C) 2000 Elsevier Science Ltd. A ll rights reserved.