Stem Cells and Development vol:21 issue:18 pages:3245-3257
In a recent study, we showed that the adult pituitary gland is capable of regenerating transgenically ablated growth hormone-producing (GH+) somatotropes. Here, we investigated whether the gland's regenerative capacity is more general and also applies to the other major hormonal cell type, the prolactin-producing (PRL+) lactotropes. We set up the transgenic PRLCre/iDTR mouse model, in which the PRL promoter drives expression of Cre that induces diphteria toxin receptor (DTR) in lactotropes. Injection of female mice with DT for different periods causes a gradual ablation of PRL+ cells, reaching a maximum of 70% after 10-day DT treatment. During the following weeks, lactotropes progressively re-appear achieving a 60% restoration after 6 weeks. The Sox2+ stem/progenitor cell compartment displays a prompt reaction to the DT-triggered cell-ablation injury, including expansion of the marginal-zone niche and co-expression of PRL, the latter only very rarely observed in control pituitary. Throughout the regeneration period (2-6 weeks), Sox2+ as well as double Sox2+/PRL+ cells continue to be more abundant than in control pituitary. In addition to this stem cell reaction, surviving or newborn lactotropes increase their proliferative activity, and bihormonal PRL+/GH+ cells become detectable suggesting somatotrope-to-lactotrope transdifferentiation. In conclusion, the adult pituitary gland is capable of restoring lactotrope cells after destruction, further confirming its regenerative competence. Repair of lactotropes appears to be driven by a combination of mechanisms, including recruitment from stem cells, proliferation of lactotropes and transdifferentiation of somatotropes.