Activated Phenotype of the Pituitary Stem/Progenitor Cell Compartment During the Early-Postnatal Maturation Phase of the Gland

The rodent pituitary gland undergoes prominent maturation during the first weeks after birth, including a wellknown increase in hormone-producing cells. In the past, it has frequently been postulated that stem cells are involved in this early-postnatal growth phase. This hypothesis can now be explored, as pituitary stem/progenitor cells were recently identified. Here, we analyzed in detail the mouse pituitary stem/progenitor cell compartment during the first postnatal week and compared its phenotype with that at the end of the first pituitary growth wave and at adult age. Stem/progenitor cells, as assessed by both side population phenotype and Sox2 expression, are most abundant at birth and gradually decline toward adulthood. The neonatal stem/progenitor cell compartment is clearly more active in terms of proliferation, stemness gene expression, and stem cell-related functional activity including sphere formation and multipotent differentiation capacity. In situ examination of pituitary sections reveals peculiar topographical arrangements of Sox2(+) cells, again more pronounced at the neonatal age. Sox2(+) cells are particularly prominent at the wedge junction of the anterior and intermediate lobe, and clusters of Sox2(+) cells appear to sprout from this and other cleft-lining, marginal zone regions. Colocalization of Sox2 and hormones is generally not observed, thus suggesting mutually exclusive expression. Together, the neonatal pituitary stem/progenitor cell compartment displays an activated phenotype, thus supporting its involvement in the early-postnatal maturation process of the gland.