title: Estradiol affects extracellular leptin:adiponectin ratio in human breast tissue in vivo.
abstract: BACKGROUND
  Exposure to sex steroids is associated with increased breast cancer risk, and adipokines, leptin and adiponectin have been implicated in cancer progression. However, it is not known whether sex steroids affect adipokine secretion in breast tissue.
  
  
  OBJECTIVE
  To elucidate the role of estrogen and tamoxifen on adipokine release in normal human breast tissue and breast cancer.
  
  
  METHODS
  Microdialysis sampling was used to collect extracellular in vivo leptin and adiponectin from normal human breast tissue in premenopausal healthy volunteers during the menstrual cycle and in postmenopausal women before tamoxifen treatment and after 6 weeks of treatment. In women with breast cancer, microdialysis was performed intratumorally before surgery. In addition, whole normal breast tissue biopsies were cultured ex vivo, and murine breast cancer models were evaluated.
  
  
  RESULTS
  In normal breast tissue, plasma estradiol negatively correlated with local extracellular adiponectin levels (r = -0.34; P < .05) and positively correlated with leptin (r = 0.37; P < .05) and leptin:adiponectin ratio (r = 0.38; P < .05). In postmenopausal women, tamoxifen treatment increased adiponectin (P < 0.05) and decreased leptin (P < .01) and the leptin:adiponectin ratio (P < .01). These in vivo results were confirmed in breast tissue biopsies cultured ex vivo. In patients with breast cancer, extracellular leptin was higher (P < .01) and adiponectin lower (P < .05) in tumors than in normal adjacent breast tissue. In a murine model of breast cancer, estrogen exposure increased leptin secretion (P < .05).
  
  
  CONCLUSIONS
  Estrogen exposure may have a critical role in the regulation of adipokines in human breast tissue and may serve as therapeutic targets for treatment and prevention.
authors.affiliation: Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Vivian
authors.initials: V
authors.lastname: Morad
authors.forename: Annelie
authors.initials: A
authors.lastname: Abrahamsson
authors.forename: Charlotta
authors.initials: C
authors.lastname: Dabrosin
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017551:Microdialysis; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism; D017697:Premenopause / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D020738:Leptin; D013629:Tamoxifen; D004958:Estradiol