Planta Med 2004; 70(1): 39-44
DOI: 10.1055/s-2004-815453
Original Paper
Biochemistry and Molecular Biology
© Georg Thieme Verlag Stuttgart · New York

Regulation of Gene Expression by 8-Prenylnaringenin in Uterus and Liver of Wistar rats

Patrick Diel3 , Renate B. Thomae1 , Antonio Caldarelli1 , Oliver Zierau1 , Susanne Kolba1 , Simone Schmidt3 , Pia Schwab2 , Peter Metz2 , Günter Vollmer1
  • 1Molekulare Zellphysiologie & Endokrinologie, Institut für Zoologie, Technische Universität Dresden, Dresden, Germany
  • 2Institut für Organische Chemie, Technische Universität Dresden, Dresden, Germany
  • 3Institut für Experimentelle Morphologie und Tumorforschung, Deutsche Sporthochschule, Köln, Germany
This paper was funded by the Deutsche Forschungsgemeinschaft Vo410/6-1 and Vo410/6-3
Further Information

Publication History

Received: July 7, 2003

Accepted: August 30, 2003

Publication Date:
06 February 2004 (online)

Abstract

The potential estrogenic activity of 8-prenylnaringenin has been investigated using several in vitro test systems. 8-Prenylnaringenin is a natural secondary product of the female blossoms of hops. The aim of the present study was to characterize 8-prenylnaringenin for its estrogenic effects in vivo. A three day uterotrophic assay was carried out on ovariectomized young female rats. A single dose of 8-prenylnaringenin (10 mg/day/kg body mass) was administered subcutaneously. 17β-Estradiol (0.03 mg/day/kg body mass; subcutaneous administration) was used as a positive control. Uterine wet weight, endometrial and vaginal epithelial height were determined by histological methods. Gene expression in uterus and in liver was assessed using realtime RT-PCR. Both estradiol and 8-prenylnaringenin significantly stimulated uterine wet weight accompanied by a proliferative response. The three day treatment resulted in a statistically significant increase of the uterine epithelial height as well as of the vaginal epithelial height, the latter being the more sensitive parameter. In the uterus of ovariectomized animals estrogen receptor-α and clusterin gene expression were down regulated following treatment with estradiol, whereas expression of complement C3 was up-regulated. In response to treatment with 8-prenylnaringenin the same gene expression pattern was detectable, but less pronounced. The levels of estrogen receptor-α mRNA in rat liver were very low and therefore could not be quantitatively assessed. Like in the uterine tissue, estradiol down regulated clusterin expression. The response to 8-prenylnaringenin was weaker but still significant. Conversely, 8-prenylnaringenin was found to be more potent than estradiol in inducing expression of IGFBP-1. In summary, the multiparametric assessment of the estrogenic activity of 8-prenylnaringenin provides overwhelming evidence that 8-prenylnaringenin has largely to be regarded as a pure estrogen agonist and is therefore a questionable candidate molecule for hormone replacement therapy.

References

Günter Vollmer

Molekulare Zellphysiologie & Endokrinologie

Institut für Zoologie

Technische Universität Dresden

Mommsenstr. 13

01062 Dresden

Germany

Phone: +49-351-463 31922

Fax: +49-351-463 39123

Email: [email protected]