title: Effects of early and late treatment with soy isoflavones in the mammary gland of ovariectomized rats.
abstract: BACKGROUND
  Soy isoflavones have been shown to be an alternative to hormone therapy at menopause, without causing side-effects such as breast cancer. However, the effects of early and late treatment with isoflavones on the mammary gland remain controversial.
  
  
  OBJECTIVE
  To investigate the effects of early and late treatment with soy isoflavones on the mammary gland of ovariectomized rats.
  
  
  METHODS
  Thirty 3-month-old rats were ovariectomized and divided equally into groups: Control, treated with vehicle solution; or with 150 mg/kg/body weight of isoflavones by gavage; or subcutaneously treated with 10 μg/kg/body weight with 17β-estradiol. Treatments started 3 days (early treatment) or 30 days (late treatment) after ovariectomy and lasted for 30 consecutive days. Thereafter, the animals were euthanized and the mammary glands were removed and processed for paraffin embedding. Sections were stained with hematoxylin and eosin for histomorphometry or subjected to immunohistochemical detection of Ki-67 and VEGF-A.
  
  
  RESULTS
  The ductal, lobular and total epithelial fractions were similar between controls and the early/late isoflavone groups, but they were significantly higher in the groups treated with estradiol. In both epithelial and stromal regions, the immunoreactivity of VEGF-A and the percentage of Ki-67-positive cells were significantly higher in the groups treated with estradiol, while they were similar in the early/late isoflavone groups and control groups.
  
  
  CONCLUSIONS
  Our results indicate that early and late treatment with soy isoflavones at the dose of 150 mg/kg/body weight does not show proliferative and angiogenic effects on the mammary gland of ovariectomized rats.
authors.affiliation: a Universidade Federal De São Paulo , São Paulo ;
authors.forename: M Aparecida
authors.initials: MA
authors.lastname: Santos
authors.affiliation: b Morphology and Genetics , Universidade Federal De São Paulo , São Paulo ;
authors.forename: R
authors.initials: R
authors.lastname: Florencio-Silva
authors.affiliation: b Morphology and Genetics , Universidade Federal De São Paulo , São Paulo ;
authors.forename: C P
authors.initials: CP
authors.lastname: Teixeira
authors.affiliation: b Morphology and Genetics , Universidade Federal De São Paulo , São Paulo ;
authors.forename: G Rodrigues da Silva
authors.initials: GR
authors.lastname: Sasso
authors.affiliation: b Morphology and Genetics , Universidade Federal De São Paulo , São Paulo ;
authors.forename: D Souza
authors.initials: DS
authors.lastname: Marinho
authors.affiliation: c Gynecology, Universidade De São Paulo , São Paulo , Brazil.
authors.forename: R S
authors.initials: RS
authors.lastname: Simões
authors.affiliation: b Morphology and Genetics , Universidade Federal De São Paulo , São Paulo ;
authors.forename: M J
authors.initials: MJ
authors.lastname: Simões
authors.affiliation: b Morphology and Genetics , Universidade Federal De São Paulo , São Paulo ;
authors.forename: A Ferraz
authors.initials: AF
authors.lastname: Carbonel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D007529:Isoflavones / Q000008:administration & dosage*; D019394:Ki-67 Antigen / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000473:pathology; D008593:Menopause; D010052:Ovariectomy; D048789:Phytoestrogens / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D007529:Isoflavones; D019394:Ki-67 Antigen; D048789:Phytoestrogens; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004958:Estradiol
keywords: Isoflavones; estrogen; mammary gland; menopause; rat