Progesterone, in addition to estrogen, induces cyclin D1 expression in the murine mammary epithelial cell, in vivo.

Previous investigations, in vitro, have demonstrated that progestins can induce the transcription of the cell cycle regulator, cyclin D1, thereby suggesting that cyclin D1 may mediate, at the molecular level, the proposed mitogenic effects of progesterone during mammary epithelial cell proliferation. To extend these initial studies into an in vivo context, comparative cyclin D1 Northern and immunohistochemical analyses were performed on mammary gland tissue isolated from wild type (WT) females as well as from the recently reported progesterone receptor knockout (PRKO) mouse model. Northern analysis revealed that estrogen induced cyclin D1 expression, 5- to 7-fold over control levels, both in the WT and PRKO female. Immunohistochemistry demonstrated that, for both test groups, the number of mammary epithelial cells expressing cyclin D1 increased significantly as compared with control values, in response to estrogen. In the case of estrogen plus progesterone treatment, Northern analysis revealed that, in the WT gland, cyclin D1 transcription increased approximately 3-fold over estrogen induced levels, an increase that was paralleled by an equivalent increase in the number of mammary epithelial cells expressing cyclin D1. Conversely, under the same hormone regimen, the PRKO mammary gland did not exhibit a further increase in cyclin D1 induction over estrogen only levels. Finally, these studies not only demonstrate that in the mammary epithelial cell, both estrogen and progesterone can induce the expression of cyclin D1 but also show that this induction correlates with mammary gland proliferation in the mouse.