Uterine effects of the phytoestrogens 8-prenylnaringenin and 6-dimethylallylnaringenin in vivo

Abstract

Phytoestrogens have been shown to exhibit significant estrogen agonistic/antagonistic effects in animals and humans. In in vitro assays for the naturally occurring flavonoids 8-prenylnaringenin (8-PN) and 6-dimethylallylnaringenin (6-DMAN) have been shown that they are potent phytoestrogenic substances. Although they differ only in the position and steric assembly of the substituent, 8-PN is shown to be the more potent substance in activating at the estrogen receptor while 6-DMAN appears to have a higher antiandrogenic potency. We tested 8-PN and 6-DMAN on their uterotrophic response in ovariectomized Wistar rats time dependent for 7h, 24h and 72h at concentrations of 15mg/kg BW. Positive control was estradiol (E2) at 10µg/kg BW and negative control was the carrier castor oil. In contrast to 8-PN 6-DMAN did not show any significant effect on uterine wet weight or stimulated the expression of proliferation markers at any time point. But entirely different from the uterotrophic response 6-DMAN stimulated uterine mRNA expression of estrogen responsive genes in the ovariectomized rats, but to a less pronounced extent than E2 and 8-PN did. Genes carrying an estrogen responsive element a 6-DMAN dependant regulation of expression could be shown. Different pattern of regulation could be resolved for genes carrying no estrogen responsive element. 8-PN and E2 regulates the expression of these genes while 6-DMAN has no effect. In conclusion, applying a time dependent protocol for the first time estrogenic activities of 6-DMAN in vivo, amazingly in contrast to estrogen gene regulation no uterine wet weight gain was observable.