We are interested in understanding extrinsic factors that regulate adult stem cell homeostasis. Identifying pathways that are unique to specific stem/progenitor cell subsets and important for their function, will afford us the opportunity to target these cells, which are currently thought to represent the cell of origin in breast cancer. Mammary stem and progenitor cells expand in response to circulating progesterone which exerts its effects through paracrine mediators such as RANKL and WNT. In this presentation, I will provide a brief overview of our recent efforts towards delineating the molecular program by which host factors including progesterone influence stem and progenitor cell pools in the mammary gland. I will discuss our recent data which shows: i) a critical link between RANK signalling and mammary WNT response; ii) a new progesterone-induced paracrine effector of mammary stem and progenitor cells; and iii) protease inhibitors to be critical regulators of adult mammary stem cell pools and ageing.