Pituitary stem cells during normal physiology and disease

Abstract

The homeostatic maintenance and functional modification of tissues require a combination of regulated proliferation and differentiation by somatic stem cells and more committed progenitors. Of relevance to regenerative medicine approaches, the endogenous stimulation of cell types for replenishment of damaged tissues requires an understanding of the signals that promote proliferation and direct appropriate differentiation to specialised cell types. We recently showed that pituitary stem cells expressing the transcription factor SOX2 are able to contribute to the generation of new hormone-producing cells during postnatal life. The signals controlling proliferation in the anterior pituitary are poorly understood and little is known about the influences supporting the choices between proliferation and quiescence among stem cells. The WNT signalling pathway is a major regulator of proliferation and influences stem cells in multiple tissues throughout the body as well as cancer stem cells in tumorigenesis. Forced up-regulation of the WNT pathway specifically in SOX2-positive pituitary stem cells by transgenic approaches in mouse stimulates a transient burst of proliferation, maintaining their uncommitted phenotype. These mutated stem cells subsequently induce tumorigenesis in a non-cell autonomous manner, as they promote proliferation of surrounding cell types through the secretion of paracrine factors. The studies presented here aim to provide insights into pituitary stem cell behaviour and their possible roles during disease states.