1. In utero and postnatal exposure to isoflavones results in a reduced responsivity of the mammary gland towards estradiol.
- Author
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Molzberger AF, Vollmer G, Hertrampf T, Möller FJ, Kulling S, and Diel P
- Subjects
- Animal Feed analysis, Animals, Breast Neoplasms prevention & control, Cell Proliferation drug effects, Estrogen Receptor alpha metabolism, Estrogen Receptor beta metabolism, Female, Gene Expression, Genistein administration & dosage, Mammary Glands, Animal metabolism, Ovariectomy, Pregnancy, Proliferating Cell Nuclear Antigen metabolism, Rats, Rats, Wistar, Environmental Exposure, Estradiol pharmacology, Isoflavones pharmacology, Mammary Glands, Animal drug effects, Postnatal Care, Prenatal Exposure Delayed Effects
- Abstract
Scope: Exposure scenarios during different stages of development of an organism are discussed to trigger adverse and beneficial effects of isoflavones (ISO). The aim of this study was to investigate how in utero and postnatal ISO exposure modulates the estrogen sensitivity of the mammary gland and to identify the underlying molecular mechanisms., Methods and Results: Therefore, rats were exposed to either ISO-free (IDD), ISO-rich (IRD) or genistein-rich diet (GRD), up to young adulthood. Proliferative activity (PCNA expression) in the mammary gland at different ages and the estrogen sensitivity of the mammary gland to estradiol (E₂) or genistein (GEN) in adult ovariectomized animals was determined and compared with different treatments. Treatment with E₂ resulted in a significant lower proliferative and estrogenic response of the mammary gland in IRD and GRD compared with IDD. This correlates to a change in the gene expression pattern and a decrease in the ratio of estrogen receptor alpha (ERα) beta (ERβ, Conclusions: Our results provide evidence that in utero and postnatal exposure to a diet rich in ISO but also to GEN reduces the sensitivity of the mammary gland toward estrogens and support the hypothesis that in utero and postnatal ISO exposure reduces the risk to develop breast cancer., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2012
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