Effects of genistein on the mammary gland proliferation of adult ovariectomised Wistar rats.
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Degen, Gisela H.
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AbstractThe effects of phytoestrogens on the female breast are discussed controversially. On the one hand, epidemiological and experimental data provide evidence that dietary phytoestrogens may prevent the development of breast cancer. On the other hand, in breast cancer cell lines and tumour models isoflavone phytoestrogens have been demonstrated to stimulate the growth of estrogen-dependent breast cancer cells. To further investigate the molecular effects of genistein (Gen) on the mammary gland, we treated non-tumour bearing, ovariectomised female Wistar rats with this phytoestrogen either subcutaneously (10 mg/kg body weight) or orally (100 and 200 mg/kg body weight) for 3 days. Estradiol (E(2), 0.004 mg/kg s. c.) and ethynylestradiol (EE, 0.1 mg/kg per os) served as reference compounds. In the breast tissue, mRNA and protein expression of the progesterone receptor (marker for estrogenicity) and PCNA (marker gene for proliferation) were examined by quantitative real-time PCR, Western blotting and immunohistochemistry; the uterotrophic response was assessed also. Treatment with Gen per os or s. c. results in a small but significant stimulation of the uterine wet weight. In the mammary gland, Gen stimulates the expression of progesterone receptor (PR) but, in contrast to E(2), the isoflavone does not stimulate the expression of PCNA. These findings resemble recent data demonstrating a differential ability of Gen to induce uterine gene expression and uterine proliferation. Our data indicate that in non-malignant breast tissue short-term administration of Gen, in contrast to more potent estrogens like E(2), does not induce proliferation. Chronic stimulation of proliferation is believed to be a key mechanism during the development of breast cancer. The limited ability of Gen to stimulate proliferation in this tissue could be an indication for a limited carcinogenic potency of Gen in the breast. In further investigations it is important to identify molecular differences between healthy and malignant breast tissue which may explain the different sensitivity towards Gen treatment.
CitationPlanta Med. 2006, 72 (4):304-310
DescriptionDietary modulation of carcinogenesis-related pathwaysDietary item or component studied: Genistein, ethynylestradiolPathways studied: gene expression and proliferation in the mammary glandStudy type (in vitro, animals, humans): wistar ratsTissue/biological material/sample size: 5μm sectionsMode of exposure (if in vivo) (acute, chronic, root of exposure): oral administrationImpact on pathway (including dose-response): after EE administration: PR expression increase in 60% of cells and PCNA expression in 70%of cells After Gen administration: not significantly induced. KEYWORDS CLASSIFICATION: administration & dosage;Administration,Oral;Animals;Blotting,Western;Cell Proliferation;drug effects;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Estradiol;Female;Genistein;Germany;Immunohistochemistry;Mammary Glands,Animal;Ovariectomy;pharmacology;Phytoestrogens;Phytotherapy;Polymerase Chain Reaction;Proliferating Cell Nuclear Antigen;Rats;Rats,Wistar;Receptors,Progesterone;Research;Rna;therapeutic use;Uterus;humans.
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- Issue date: 2007 Dec
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- Issue date: 2004 Jun 30
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- Issue date: 2010 Jul 15
- Hormonal activity of combinations of genistein, bisphenol A and 17beta-estradiol in the female Wistar rat.
- Authors: Schmidt S, Degen GH, Seibel J, Hertrampf T, Vollmer G, Diel P
- Issue date: 2006 Dec
- The bone-protective effect of the phytoestrogen genistein is mediated via ER alpha-dependent mechanisms and strongly enhanced by physical activity.
- Authors: Hertrampf T, Gruca MJ, Seibel J, Laudenbach U, Fritzemeier KH, Diel P
- Issue date: 2007 Jun