Stem cells in the pituitary gland: A burgeoning field.

The pituitary gland represents the endocrine core of the organism, and is well-known for its cellular plasticity in order to meet the body's fluctuating hormonal demands. In the past, it has repeatedly been postulated that the pituitary harbors tissue-specific stem cells that participate in the generation of new endocrine cells during this dynamic cell remodeling, as well as during the slow but robust homeostatic turnover of the gland. However, their presence and identity remained elusive until this conundrum recently attracted renewed interest. Our discovery of a 'side population' using flow cytometry was the first step towards a more convincing candidate stem/progenitor cell population in the endocrine anterior pituitary. Since then, several other groups have endeavored to search for pituitary stem/progenitor cells, which finally culminated in the identification of very strong candidates. Multiple markers were put forward, among which the pluripotency transcription factor Sox2 occupies center stage. Now that very plausible pituitary stem/progenitor cells can be isolated and assayed, detailed characterization of their involvement in pituitary cell remodeling during basal renewal, dynamic adaptation and potential response to injury is around the corner, and is expected to significantly advance our knowledge on pituitary biology. In addition, a comprehensive study of the stem/progenitor cells may guide us to a better understanding of pituitary hormonal deficiencies, as well as of pituitary tumorigenesis in which 'cancer stem cells' may play a central role. Nevertheless, many questions remain to be resolved, and future challenges are huge. In this review, we provide a detailed overview of the exciting recent developments in the pituitary stem cell quest. In addition we pinpoint some discordant findings and include a number of cautionary and critical reflections. The recent acceleration in pituitary stem cell research may initiate a very exciting era in the pituitary field. May we say that "La nouvelle hypofyse est arrivée"?