Endocrine Abstracts

Dysfunction in the mechanisms that regulate cell numbers in the pituitary gland can underlie hypopituitarism as well as the generation of tumours. Investigations into how these conditions arise has led to an interest in identifying mechanisms for correct maintenance of endocrine cells throughout life. Currently, the source and identity of signals promoting this maintenance in the postnatal pituitary are not known. We have previously shown that pituitary-specific disruptions in the WNT signalling pathway, a key developmental pathway often perturbed in disease including cancer, can lead to developmental anomalies and tumorigenesis. Here, we provide in vivo evidence that WNT signals promote the generation of new cells in the anterior pituitary. Using genetic lineage tracing in mouse we show that SOX2-expressing cells act as stem cells in vivo, able to differentiate into all hormone-producing lineages and contribute to organ homeostasis during postnatal life. However, SOX2-expressing stem cells are not the sole source of new endocrine cells at these stages, but complement contribution from more committed cell types. We find that committed cells responding to WNT signals are capable of proliferation and provide the majority of organ turnover. Unexpectedly, we uncover that SOX2-expressing stem cells act as critical regulators of this process through secreting WNT ligands promoting proliferation, thus influencing long-term physiological cell turnover in a paracrine manner. This represents a key step towards understanding the mechanisms controlling stimulation of new cell generation in situ, with an impact on future therapies for diseases of the pituitary gland.