Comparative Study on the Nuclear Hormone Receptor Activity of Various Phytochemicals and Their Metabolites by Reporter Gene Assays Using Chinese Hamster Ovary Cells

Phytochemicals are naturally present in a wide variety of plants, and have been suggested to exert a number of effects beneficial to human health. Several phytochemicals possess estrogenic activity through estrogen receptor alpha (ER alpha) and ER beta, and are, therefore, termed phytoestrogens. In this study, we examined whether various phytochemicals have agonistic and/or antagonistic activity against six human nuclear receptors (ER alpha, ER beta, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor alpha(1) (TR alpha(1)) and TR beta(1)) by in vitro reporter gene assays using Chinese hamster ovary cells. Of the 31 phytochemicals tested, including flavonoids, isoflavonoids, coumestan, lignans, catechins and their metabolites, 20 compounds showed estrogenic activity via ER alpha and/or ER beta, and we ranked these phytochemicals according to their estrogenic potency via ER alpha and ER beta. As a result, coumestrol and genistein strongly activated ER alpha and ER beta at very low concentrations of < 1 x 10(-10) M. Most phytochemicals showing estrogenic activity also exhibited agonistic activity against ER beta at lower concentrations than those for ER alpha, and two typical isoflavones, genistein and daidzein, in particular, showed a potent preference for ER beta. Further, we found that baicalein has ER beta antagonistic activity, and two compounds, enterolacton and O-desmethylangolensin, have AR antagonistic activity. Nevertheless, none of tested compounds showed AR agonistic activity together with GR, TR alpha(1) and TR beta(1) agonistic/antagonistic activity. These results suggest that various phytochemicals or their metabolites preferentially interact with ER alpha/beta among the six nuclear hormone receptors tested, and that the ER beta agonistic activity, in particular, of these compounds may he associated with various beneficial effects on human health.