@article{oai:repo.qst.go.jp:00046436,
 author = {Imaoka, Tatsuhiko and Hisatune, Hiromi and Sakanishi, Yoshimi and Nishimura, Yukiko and Nishimura, Mayumi and Shimada, Yoshiya and 今岡 達彦 and 久恒  裕美 and 坂西 良彌 and 西村 由希子 and 西村 まゆみ and 島田 義也},
 issue = {9},
 journal = {Journal of Endocrinological Investigation},
 month = {Oct},
 note = {Background: Long-lived somatic cells such as stem/progenitor cells may progressively accumulate oncogenic mutations and cause cancer. Some evidence suggests that premenopausal administration of progesterone confers a long-term increased risk of breast cancer. 
Aim: To clarify the effect of progesterone on long-lived mammary epithelial cells in rats. 
Materials and Methods: Female Sprague-Dawley rats (3 and 7 weeks of age) were implanted subcutaneously 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 [LRECs] 10 weeks after BrdU labeling in both mammary lobules and ducts. Treatment with progesterone during labeling significantly increased the fraction of long-lived LRECs 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.},
 pages = {828--834},
 title = {Progesterone stimulates proliferation of a long-lived epithelial cell population in rat mammary gland},
 volume = {35},
 year = {2012}
}