Uterine effects of the phytoestrogen 6-(1,1-dimethylallyl)naringenin in rats.
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.
Zierau
Oliver
O
Institut für Zoologie, Technische Universität Dresden, Zellescher Weg 20, EG, Raum 28a, 01217 Dresden, Germany. Oliver.Zierau@mailbox.tu-dresden.de
Geis
Renate-B
RB
Tischer
Sandra
S
Schwab
Pia
P
Metz
Peter
P
Vollmer
Günter
G
D000818:Animals; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D005260:Female; D044950:Flavanones / Q000008:administration & dosage / Q000494:pharmacology*; D019833:Genistein; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology; D010052:Ovariectomy; D048789:Phytoestrogens; D008517:Phytotherapy; D028321:Plant Preparations / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000187:drug effects*
C462031:6-(1,1-dimethylallyl)naringenin; D017931:DNA Primers; D044950:Flavanones; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D019833:Genistein