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Guillermo Rimoldi, Julie Christoffel, Dana Seidlova-Wuttke, Hubertus Jarry, and Wolfgang Wuttke

Department of Clinical and Experimental Endocrinology, Georg-August-University, Göttingen, Germany

Abstract
Background: The isoflavone genistein (GEN) is found in soy (Glycine max) and red clover (Trifolium pratense) . The estrogenic activity of GEN is known, and it is widely advertised as a phytoestrogen useful in alleviating climacteric complaints and other postmenopausal disorders. Knowledge of effects of long-term administration of GEN in laboratory animals is scarce, and effects in the uterus and mammary gland after long-term administration have not been studied. The uterus and mammary gland are known to be negatively influenced by estrogens used in hormone therapy.

Objectives: We administered two doses of GEN [mean daily uptake 5.4 (low) or 54 mg/kg (high) body weight (bw) ] orally over a period of 3 months to ovariectomized (ovx) rats and compared the effects with a treatment with two doses of 17β-estradiol [E₂ ; 0.17 (low) or 0.7 mg/kg bw (high) ]. Mammary glands, vaginae, and uteri were investigated morphologically and immunohistochemically. We quantified the expression of proliferating cell nuclear antigen (PCNA) and progesterone receptor (PR) in the mammary gland.

Results: In rats treated with either of the E₂ doses or the high GEN dose, we found increased uterine weight, and histologic analysis showed estrogen-induced features in the uteri. In vaginae, either E₂ dose or GEN high induced hyperplastic epithelium compared with the atrophic controls. In the mammary gland, E₂ (either dose) or GEN increased proliferation and PR expression. Serum levels of luteinizing hormone were decreased by E₂ (both doses) but not by GEN.

Conclusions: In summary, E₂ and GEN share many effects in the studied organs, particularly in the vagina, uterus, and mammary gland but not in the hypothalamo/pituitary unit.

Key words: estradiol, genistein, mammary gland, uterus, vagina. Environ Health Perspect 115(suppl 1) : 62–68 (2007) . doi:10.1289/ehp.9367 available via http://dx.doi.org/ [Online 8 June 2007]

Address correspondence to W. Wuttke, Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany. Telephone: 49 551 396714. Fax: 49 551 396518. E-mail: ufkendo@med.uni-goettingen.de

This article is part of the monograph "Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects."

This study was funded in part by the European Union (EURISKED contract EVK1-CT-2002-00128 and CASCADE contract Food-CT-2004-506319) .

The author declares he has no competing financial interests.

Received 22 May 2006 ; accepted 30 October 2006.