Estrogenic Activity in White and Red Wine Extracts

Abstract

Red wine is enriched in resveratrol, trans-3,5,4'-trihydroxystilbene, a compound in grape skin that inhibits the development of pre-neoplastic lesions in mouse mammary tumor cells in culture and inhibits cancer cell proliferation in vitro. Grapes also contain other bioactive compounds including flavonoids, flavans, and anthocyanins. The estrogenic activities of extracts prepared from one white (Freie Weingärtner Wachau, Grüner Veltliner, Austria) and two red wines (Woodbridge, Cabernet Sauvignon, California; and Lenz Moser Prestige, Blaufränkisch Barrique, Austria) were examined and compared with those induced by estradiol (E(2)) and trans-resveratrol. First, the estrogenic activity of the wine extracts was evaluated in a yeast estrogen screen (YES) assay, in which yeast express copper-inducible estrogen receptor alpha (ERalpha) and an estrogen-response-element (ERE)-driven beta-galactosidase reporter. In YES, the white wine extract showed no estrogenic activity. In contrast, both of the red wine extracts showed estrogenic activity equivalent to that of 0.2 nM E(2). Similarly, the white wine extract showed no transcriptional activity with either ERalpha and ERbeta in transiently transfected CHO-K1 cells. In contrast, both red wine extracts stimulated ERE-reporter activity in a concentration-dependent manner that was inhibited by 4-hydroxytamoxifen (4-OHT), indicating that the observed transcriptional activity was ER-mediated. The red wine extracts showed significantly higher ERbeta versus ERalpha agonist activity. Resveratrol showed no agonist activity in YES but activated ERalpha and ERbeta in CHO-K1 cells in a concentration-dependent manner that was inhibited by 4-OHT. This indicates that resveratrol requires mammalian cell components that are absent in yeast for estrogen agonist activity, whereas the estrogenic activity of wine extracts is directly through ERalpha and does not require mammalian cell factors such as coactivators. The estrogenic activity in red wine found by using YES indicates that estrogenic compounds other than resveratrol are present. Chemical analysis clearly showed that the trans-resveratrol content of the red wine extracts was 1 order of magnitude below the detection limit for YES assay.

Endocrine disruptors in bottled mineral water: total estrogenic burden and migration from plastic bottles

“…Klinge et al (2003) detected a maximum 84 ng/l EEQ in red wine. Promberger et al (2001) calculated 23-41 ng/l EEQ for beer, a result that was confirmed by Takamura-Enya et al (2003), who detected an estrogenic potency of approximately 30 ng/l EEQ in beer; extracts from soy based food (miso, tofu, and soy sauce) and coffee also contained EEQ in low nanogram per liter range.…”

The Effects of Biological Sex and Diet on the Development of Heart Failure

“…However, resveratrol was originally characterized as a phytoestrogen on the basis of its ability to bind ERs. 166 Because studies indicate that an average consumer is capable of absorbing physiological quantities of resveratrol from normal red wine intake, molecular characterization is necessary. Resveratrol exists as cis-and trans-isomers; the trans-isomer mediates most of its biological actions.…”

“…168 Resveratrol demonstrates genomic activity as indicated by activation of an ERE-luciferase reporter in transiently transfected Chinese hamster ovary K1 (CHO-K1) cells but shows higher activation with ER␤ than ER␣ consistent with other phytoestrogen compounds like genistein. 166 Nongenomic activity of resveratrol has also been described. In a recent study, resveratrol inhibited androgenand ER␣-dependent PI3-K activities in prostate cancer cell lines.…”

Anti-atherogenic effects of resveratrol

“…Furthermore, RS inhibits the enzyme cyclooxygenase-1, which is a strong vasoconstrictor and has an important role in platelet aggregation (Szewczuk et al, 2004). Increased activity of nitric oxide synthase was found in pulmonary artery endothelial cells when treated with RS, which indicates the direct association of nitric oxide in vasorelaxation (Klinge et al, 2003). RS has been shown to increase the expression of nitric oxide synthase and hence, potentially protect perfused working hearts (Hattori et al, 2002), although RS failed to show such protective effect in nitric oxide synthase knockout mice (Imamura et al, 2002).…”