title: In utero and postnatal exposure to isoflavones results in a reduced responsivity of the mammary gland towards estradiol.
abstract: METHODS
  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.
  
  
  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.
authors.affiliation: Department of Molecular and Cellular Sports Medicine, German Sports University Cologne, Germany. a.molzberger@googlemail.com
authors.forename: Almut F
authors.initials: AF
authors.lastname: Molzberger
authors.forename: Günter
authors.initials: G
authors.lastname: Vollmer
authors.forename: Torsten
authors.initials: T
authors.lastname: Hertrampf
authors.forename: Frank Josef
authors.initials: FJ
authors.lastname: Möller
authors.forename: Sabine
authors.initials: S
authors.lastname: Kulling
authors.forename: Patrick
authors.initials: P
authors.lastname: Diel
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D001943:Breast Neoplasms / Q000517:prevention & control; D049109:Cell Proliferation / Q000187:drug effects; D004781:Environmental Exposure; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019833:Genistein / Q000008:administration & dosage; D007529:Isoflavones / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D011181:Postnatal Care; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D018809:Proliferating Cell Nuclear Antigen; D004958:Estradiol; D019833:Genistein