Unraveling the biology and functional significance of pituitary stem cells as a basis towards restorative therapies in pituitary hormone deficiencies

 The pituitary is our master endocrine gland controlling vital physiological processes like growth, metabolism, stress and reproduction. In addition to hormone-producing cells, the gland also harbors a population of stem cells whose role remains largely unknown. The adult pituitary’s stem cells appear highly dormant. However, the population is promptly activated upon injury in the gland, as a first step toward subsequent tissue regeneration. The stem cell compartment is also activated during the gland’s neonatal maturation. How pituitary stem cell activation occurs is unknown. Recently, we developed 3D organoids as novel, state-of-the-art in vitro research tools to query pituitary stem cell biology. We found that activated pituitary stem cells give rise to more abundant organoids of particular (cystic) morphology. Interestingly, our preliminary research advanced interleukin-6 (IL-6) as a strong-candidate key factor underlying pituitary stem cell activation. Here, we undertake a profound inquiry into the role of the IL-6 pathway in pituitary stem cell activation using our novel organoid models, followed by in vivo translation in mouse. Enlightening the black box of pituitary stem cell activation will be vital to understand pituitary (patho-)biology, regeneration and aging (with fading stem cell fitness). Ultimately, our study may guide to new stem cell-driven regenerative therapies for patients with damaged (or aged) pituitary and resultant life-burdening hormonal deficiencies.