Uterine effects of the phytoestrogen 6-(1,1-dimethylallyl)naringenin in rats.

Abstract:

:Phytoestrogens are discussed as candidate substances to treat symptoms related to estrogen deficiency. In in vitro experiments, the naturally occurring flavonoid 6-(1,1-dimethylallyl)naringenin (6-DMAN) emerged as one of the most potent phytoestrogenic substances. 6-DMAN is not as well characterized as other flavonoids (8-prenylnaringenin) or isoflavones (genistein). We tested 6-DMAN for the first time in vivo, in a dose-dependent three-day uterotropic assay in ovariectomized Wistar rats, using 6-DMAN at three different concentrations (1.5 mg/kg; 7.5 mg/kg and 15 mg/kg BW/d). Estradiol (E2; 10 microg/kg BW/d) and the carrier castor oil were used as positive and negative controls. 6-DMAN did not have any effect on uterine wet weight, while the positive control E2 did. In contrast, 6-DMAN stimulated uterine mRNA expression of estrogen responsive genes in ovariectomized rats. Estrogen receptor alpha and beta mRNA were expressed in the uterus. They mediate the expression of genes with an estrogen responsive element in the promoter, e. g., complement C3 and the progesterone receptor. Therefore, we analyzed the expression of the above-mentioned genes in three different concentrations. 6-DMAN up-regulated progesterone receptor and particularly complement C3 mRNA expression however, less pronounced than E2. In conclusion, we demonstrated for the first time estrogenic activities of 6-DMAN in vivo. Surprisingly, although 6-DMAN regulated estrogen responsive gene expression, there was no uterine wet weight gain. These findings make 6-DMAN a very interesting candidate substance for further characterization, as it potentially represents a naturally occurring selective estrogen receptor modulator.

journal_name

Planta Med

journal_title

Planta medica

authors

Zierau O,Geis RB,Tischer S,Schwab P,Metz P,Vollmer G

doi

10.1055/s-2004-827178

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

590-3

issue

7

eissn

0032-0943

issn

1439-0221

journal_volume

70

pub_type

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