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 μg/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 α and β 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.
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Dr. Oliver Zierau
Institut für Zoologie
Technische Universität Dresden
Zellescher Weg 20, EG, Raum 28a
01217 Dresden
Germany
Telefon: +49-351-4633-7841
Fax: +49-351-4633-1923
eMail: Oliver.Zierau@mailbox.tu-dresden.de
