Female reproductive hormones control mammary gland morphogenesis,In the abs
ence of the progesterone receptor (PR) from the mammary epithelium, ductal
side-branching fails to occur. We can overcome this defect by ectopic expre
ssion of the protooncogene Wnt-1. Transplantation of mammary epithelia from
Wnt-4(-)/(-) mice shows that Wnt-4 has an essential role in side-branching
early in pregnancy. PR and Wnt-4 mRNAs colocalize to the luminal compartme
nt of the ductal epithelium. Progesterone induces Wnt-4 in mammary epitheli
al cells and is required for increased Wnt-4 expression during pregnancy. T
hus, Wnt signaling is essential in mediating progesterone function during m
ammary gland morphogenesis.