Progesterone signaling and mammary gland morphogenesis

Progesterone was identified as a mammogenic hormone several years ago but until now its precise role in mammary development has remained obscure. Recently with the generation of several transgenic mouse models and development of reagents for analysis of progesterone receptor expression, the role of progesterone signaling in mammary development is becoming more clear. The most significant observations to emerge from these studies are (1) progesterone receptors (PR)(4) are present in a heterogeneous manner in the epithelial cells and undetectable in the surrounding fat pad; (2) they are essential for lobuloalveolar and not for ductal morphogenesis; (3) progesterone signaling through progesterone receptors, leading to lobuloalveolar development, is initiated in the epithelium and may occur through paracrine mechanisms; and (4) a regulated expression of the two isoforms of progesterone receptor is critical for maintaining appropriate responsiveness to progesterone and hence, epithelial cell replicative homeostasis. These studies also reveal that the consequences of progesterone signaling through progesterone receptor may depend on the cell context, cell-cell and cell-extracellular matrix interactions, the dynamics of PR turnover and the fate of PR positive cells.