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Overlapping and Distinct Expression of Progesterone Receptors A and B in Mouse Uterus and Mammary Gland during the Estrous Cycle

Westmead Institute for Cancer Research (P.A.M., R.L.A.-M., N.G., A.deF., C.L.C.), University of Sydney at the Westmead Millennium Institute, and Department of Gynecological Oncology (N.G., A.deF.), Westmead Hospital, Westmead, New South Wales 2145, Australia; and Department of Molecular and Cellular Biology (B.M.-J., O.M.C.), Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Dr. Patricia Mote, Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead, New South Wales 2145, Australia. E-mail: patricia_mote{at}wmi.usyd.edu.au.

In rodents, progesterone receptors (PRs) A and B have different and often nonoverlapping roles, and this study asked whether different activities of the PR proteins in mouse are related to differences in their expression in reproductive tissues. The individual expression of PRA and PRB was determined immunohistochemically in mammary gland and uterus during the estrous cycle or in response to endocrine manipulation. In the mammary gland, PRA and PRB were colocated in PR+ epithelial cells, with little change during the estrous cycle. In the uterus, PRA was not detected in luminal epithelium at any stage of the cycle, and PR+ luminal cells expressed only PRB. In the stroma and myometrium, PRA and PRB levels fluctuated with cyclical systemic hormone exposure. Observation of functional end points suggested that augmented stromal and/or myometrial PRA in proestrus inhibited estrogen receptor expression and epithelial proliferation. Colocation of PRA and PRB was hormonally regulated, and ovariectomy did not reproduce the expression of PRA and PRB in the uterus during the estrous cycle. Whereas PRB was the only PR in the luminal epithelium in cycling mice, ovariectomy restored PRA expression, resulting in PRA-PRB colocation. In stroma and myometrium, PRA and PRB colocated in PR+ cells, but ovariectomy reduced PRA levels more than PRB, resulting in PRB-only-expressing cells. This study has shown that nonoverlapping PRA and PRB expression in the uterus, in particular the lack of PRA, and expression of PRB only in the luminal epithelium throughout the estrous cycle, is likely to contribute to the distinct roles of PRA and PRB in the adult mouse.

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