A sharp and sustained rise in circulating estrogen and its presumably positive effect on expression of several genes involved in regulating the transition between proliferative and differentiating cellular phenotypes (MMP1, ADM, AREG, GJA1, RUNX2: all found here to be up-regulated in CF, see Figure 2) might be a key factor in determining the equilibrium between these two states in the female CF airway epithelium. Here, GJA1 is linked to cystic fibrosis.