title: Progesterone stimulates proliferation of a long-lived epithelial cell population in rat mammary gland.
abstract: BACKGROUND
  Long-lived somatic cells such as stem/progenitor cells may progressively accumulate oncogenic mutations and cause cancer. Some evidence suggests that pre-menopausal administration of progesterone confers a long-term increased risk of breast cancer.
  
  
  OBJECTIVE
  To clarify the effect of progesterone on long-lived mammary epithelial cells in rats.
  
  
  METHODS
  Female Sprague- Dawley rats (3 and 7 weeks of age) were implanted sc with 14-day slow-release pellets of 5-bromo-2'-deoxyuridine (BrdU) and were sacrificed every 2 weeks between 0 and 10 weeks after the release period. Some rats at 7 weeks of age were also implanted with progesterone and sacrificed 0 or 10 weeks after the release period. Mammary glands were examined by immunohistochemistry and immunofluorescence for BrdU, proliferative cell nuclear antigen (PCNA) and progesterone receptor (PR).
  
  
  RESULTS
  After BrdU labeling of 3- and 7-week-old rats, the BrdU index decreased gradually over 10 weeks and resulted in small fractions (1-3%) of label-retaining epithelial cells (LREC) 10 weeks after BrdU labeling in both mammary lobules and ducts. Treatment with progesterone during labeling significantly increased the fraction of long-lived LREC in lobules and ducts by 9- and 4-fold, respectively. The long-lived LREC population in the ducts was enriched for PCNA- and PR-positive cells, but the percentage of positive cells was not affected by progesterone in either lobules or ducts.
  
  
  CONCLUSIONS
  Progesterone stimulates proliferation of a long-lived epithelial cell population in the mammary lobules and ducts of rats. Such cells in the duct are characterized by a high proliferation rate and PR expression.
authors.affiliation: Radiobiology for Children's Health Program, Research Center for Radiation Protection, National Institute of Radiological Sciences, Chiba, Japan. t_imaoka@nirs.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Imaoka
authors.forename: H
authors.initials: H
authors.lastname: Hisatsune
authors.forename: Y
authors.initials: Y
authors.lastname: Sakanishi
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011980:Receptors, Progesterone / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011372:Progestins; D018809:Proliferating Cell Nuclear Antigen; D011980:Receptors, Progesterone; D011374:Progesterone; D001973:Bromodeoxyuridine