Human Reproduction, Vol. 16, No. 5, 997-1006,
May 2001
© 2001 European Society of Human Reproduction and Embryology
Phytoestrogens and carcinogenesis—differential effects of genistein in experimental models of normal and malignant rat endometrium
1 Institut für Experimentelle Morphologie und Tumourforschung, Deutsche Sporthochschule, Köln and 2 Molekulare Zellphysiologie und Endokrinologie, Institut für Zoologie, Technische Universität, Dresden, Germany
The phytoestrogen genistein was studied in normal and malignant experimental uterine models in vivo. The action of genistein on the uterus and vagina of ovariectomized DA/Han rats after 3 day oral administration (25, 50 or 100 mg/kg/BW/d) was compared to ethinyl oestradiol (0.1 mg/kg/BW/d). Effects on uterine and vaginal morphology, uterine growth and uterine gene expression were studied. A dose dependent increase of the uterine wet weight and the uterine and vaginal epithelial height, a dose dependent up-regulation of complement C3, down-regulation of clusterin mRNA expression and a stimulation of the vaginal cornification was observed after administration of genistein. Uterine gene expression and vaginal epithelium respond to genistein at doses where no significant effects on uterine wet weight were detectable. In general the vagina was more sensitive to genistein than the uterus. To analyse the action of genistein in malignant uterine tissue, the impact of a 28 d treatment with 50 mg/kg/d of genistein on the in-vivo tumour growth of RUCA I endometrial adenocarcinoma cells, following subcutaneous inoculation into syngeneic DA/Han rats, was assessed. In contrast to ethinyl oestradiol (0.1 mg/kg/BW/d), a dose of 50 mg/kg/BW/d of genistein did not affect tumour growth. Nevertheless C3 and TRPM2 mRNA expression in the tumour were both significantly stimulated by ethinyl oestradiol and genistein. In comparison to ovariectomized animals genistein up-regulated uterine wet weight and uterine dependent gene expression in tumour bearing animals. In conclusion, four independent uterine and vaginal parameters indicate genistein is a weak oestrogen receptor agonist in the uterus and vagina of female DA/Han rats, and evidence is provided for a selective oestrogen receptor modulator (SERM)-like action of genistein in normal and malignant uterine tissue.
Key words: endometrial adenocarcinoma/gene expression/phytoestrogen/rat model/uterus
3 To whom correspondence should be addressed at: Molekulare Zellphysiologie und Endokrinologie, Institut für Zoologie, Technische Universität Dresden, Mommsen Str. 13, 01062 Dresden, Germany. E-mail: guenter.vollmer{at}mailbox.tu-dresden.de
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. M Davis, J. Mao, B. Naz, J. A Kohl, and C. S Rosenfeld Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus J. Mol. Endocrinol., October 1, 2008; 41(4): 205 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Akbas, X. Fei, and H. S. Taylor Regulation of HOXA10 expression by phytoestrogens Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E435 - E442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. A. Salvo, S. M. Boue, J. P. Fonseca, S. Elliott, C. Corbitt, B. M. Collins-Burow, T. J. Curiel, S. K. Srivastav, B. Y. Shih, C. Carter-Wientjes, et al. Antiestrogenic Glyceollins Suppress Human Breast and Ovarian Carcinoma Tumorigenesis Clin. Cancer Res., December 1, 2006; 12(23): 7159 - 7164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Ford Jr., S. G. Clark, E. M. Walters, M. B. Wheeler, and W. L. Hurley Estrogenic effects of genistein on reproductive tissues of ovariectomized gilts J Anim Sci, April 1, 2006; 84(4): 834 - 842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-K. Kim, C. Nelson-Dooley, M. A. Della-Fera, J.-Y. Yang, W. Zhang, J. Duan, D. L. Hartzell, M. W. Hamrick, and C. A. Baile Genistein Decreases Food Intake, Body Weight, and Fat Pad Weight and Causes Adipose Tissue Apoptosis in Ovariectomized Female Mice J. Nutr., February 1, 2006; 136(2): 409 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Jefferson, R. Newbold, E. Padilla-Banks, and M. Pepling Neonatal Genistein Treatment Alters Ovarian Differentiation in the Mouse: Inhibition of Oocyte Nest Breakdown and Increased Oocyte Survival Biol Reprod, January 1, 2006; 74(1): 161 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. N. Jefferson, E. Padilla-Banks, and R. R. Newbold Adverse Effects on Female Development and Reproduction in CD-1 Mice Following Neonatal Exposure to the Phytoestrogen Genistein at Environmentally Relevant Doses Biol Reprod, October 1, 2005; 73(4): 798 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kim, I. Sohn, Y. S. Lee, and Y. S. Lee Hepatic Gene Expression Profiles Are Altered by Genistein Supplementation in Mice with Diet-Induced Obesity J. Nutr., January 1, 2005; 135(1): 33 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Unfer, M. L. Casini, L. Costabile, M. Mignosa, S. Gerli, and G. C. Di Renzo High Dose of Phytoestrogens Can Reverse the Antiestrogenic Effects of Clomiphene Citrate on the Endometrium in Patients Undergoing Intrauterine Insemination: A Randomized Trial Reproductive Sciences, July 1, 2004; 11(5): 323 - 328. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Naaz, S. Yellayi, M. A. Zakroczymski, D. Bunick, D. R. Doerge, D. B. Lubahn, W. G. Helferich, and P. S. Cooke The Soy Isoflavone Genistein Decreases Adipose Deposition in Mice Endocrinology, August 1, 2003; 144(8): 3315 - 3320. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Piersen Phytoestrogens in Botanical Dietary Supplements: Implications for Cancer Integr Cancer Ther, June 1, 2003; 2(2): 120 - 138. [Abstract] [PDF]
|
|
|
|
 |
|
 U. A. Kayisli, C. A. H. Aksu, M. Berkkanoglu, and A. Arici Estrogenicity of Isoflavones on Human Endometrial Stromal and Glandular Cells J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5539 - 5544. [Abstract] [Full Text] [PDF]
|
|