Murine progesterone receptor expression in proliferating mammary epithelial cells during normal pubertal development and adult estrous cycle: Association with ER alpha and ER beta status

The ovarian steroids estrogen and progesterone are important in directing t he normal growth and development of the mouse mammary gland. Previously, we have demonstrated that the majority of proliferating mammary epithelial ce lls do not express estrogen receptor-alpha (ER alpha). In this study we exa mined the relationship between progesterone receptor (PR) expression and pr oliferation in mammary epithelial cells using simultaneous immunohistochemi stry for progesterone receptor (PR) and tritiated thymidine [H-3]-Tdr) auto radiography. Results showed that the majority (>80%) of mammary epithelial cells labeled with [H-3]-Tdr were PR-positive in the terminal end buds (TEB s) of pubertal mice and the ducts of pubertal and adult mice. Whereas the m ajority of mammary epithelial cells were also PR-positive, the basal cell p opulation, which comprises the minority of mammary epithelial cells in the mammary ducts, was predominantly PR-negative. Nevertheless, the PR-positive phenotype remained the major proliferating cell type in the basal populati on. These findings suggest that the progesterone signaling pathway is invol ved in the proliferation of basal cell populations, potentially directing f ormation of tertiary side branching during pubertal development and alveola r bud formation in adult glands. A proportion of the basal cells exhibited weak expression of ER beta, suggesting that the role of ER beta in mediatin g normal estrogen-induced responses should be further studied.