Extensive remodelling of the mammary gland during pregnancy generates milk-producing lobuloalveolar structures. During remodelling, multipotent stem cells proliferate and differentiate into lineage-committed progenitor cells, which subsequently differentiate into mature epithelial cell types. It has been proposed that progesterone drives mammary stem cell expansion during pregnancy via paracrine signalling from progesterone receptor-positive sensor cells. On , Christopher Ormandy and colleagues investigate how the resulting cells are directed towards the secretory lineage. Progesterone induces the expression of the transcription factor Elf5 in mouse mammary progenitor cells, they report, and Elf5 (which is essential for progenitor cell differentiation) cooperates with progesterone to promote alveolar development. They show that the progesterone receptor and Elf5 are expressed in different cell types, and identify the transcriptional activator RankL as the paracrine mediator of progesterone’s effects on Elf5 expression in progenitor cells and their consequent differentiation. RankL also mediates the progesterone-induced division of mammary stem cells. Together, these findings reveal how steroid hormones drive mammary gland remodelling during pregnancy.
