Figure 7.

Effect of GH Stimulation on Normal Mammary Stem/Progenitor Cells and Implications for Oncogenic Transformation: A Model

(A) Normal mammary stem cells undergo asymmetric divisions, which generate a stem cell that goes into quiescence and a proliferating progenitor that gives rise to differentiated progenies. In the presence of GH, the daughter cell destined to become quiescent divides again, doubling the final total number of progenies.

(B) GH is part of an intercellular signaling loop triggered by E2, which drives expression of PR, followed by P4/PR signaling and local production of GH. This signaling loop is active as long as steroid hormones levels are elevated (puberty, middle of the menstrual cycle, pregnancy) and results in an increased number of stem/progenitor cells entering the cell cycle, through GH/GHR activation.

(C) Increased levels or prolonged exposure steroid hormones and/or GH would lead eventually to an expanded undifferentiated population at a higher risk for transformation through oncogenic hits.