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Submitted on March 22, 2005
Accepted on April 28, 2005
Department of Physiologyand the Cell and Molecular Biology Program, Michigan State University, East Lansing MI, 48824
* To whom correspondence should be addressed. E-mail: shaslam{at}msu.edu.
Progesterone (P) is a potent mitogen in the mammary gland. Based on studies using cells and animals engineered to express progesterone receptor (PR) isoforms A or B, PRA and PRB are believed to have different functions. Using an immunohistochemical approach with antibodies specific for PRA only or PRB only, we show that PRA and PRB expression in mammary epithelial cells are temporally and spatially separated during normal mammary gland development in the Balb/c mouse. In the virgin mammary gland when ductal development is active the only PR protein isoform expressed was PRA. PRA levels were significantly lower during pregnancy, suggesting a minor role at this stage of development. PRB was abundantly expressed only during pregnancy, during alveologenesis. PRA and PRB colocalization occurred in only a small percentage of cells. During pregnancy there was extensive colocalization of PRB with BrdU and cyclin D1; 95% of BrdU positive cells and 83% of cyclin D1 positive cells expressed PRB. No colocalization of PRA with either BrdU or cyclin D1 was observed at pregnancy. In the virgin gland PRA colocalization with BrdU or cyclin D1 was low; only 27% of BrdU positive cells and 4% of cyclin D1 positive cells expressed PRA. The implication of these findings is that different actions of P are mediated in PRB positive vs. PRA positive cells in vivo. The spatial and temporal separation of PR isoform expression in mouse mammary gland provides a unique opportunity to determine the specific functions of PRA vs. PRB in vivo.
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