Progesterone signaling and mammary gland morphogenesis

Progesterone was identified as a mammogenic hormone several years ago but u ntil now its precise role in mammary development has remained obscure. Rece ntly 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 m ost significant observations to emerge from these studies are (1) progester one receptors (PR)(4) are present in a heterogeneous manner in the epitheli al cells and undetectable in the surrounding fat pad; (2) they are essentia l for lobuloalveolar and not for ductal morphogenesis; (3) progesterone sig naling through progesterone receptors, leading to lobuloalveolar developmen t, is initiated in the epithelium and may occur through paracrine mechanism s; and (4) a regulated expression of the two isoforms of progesterone recep tor is critical for maintaining appropriate responsiveness to progesterone and hence, epithelial cell replicative homeostasis. These studies also reve al that the consequences of progesterone signaling through progesterone rec eptor may depend on the cell context, cell-cell and cell-extracellular matr ix interactions, the dynamics of PR turnover and the fate of PR positive ce lls.