Pituitary stem cell regulation: who is pulling the strings?

Abstract

The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells, which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory. Since postnatal stem cells in general reiterate embryonic developmental pathways, attention is first being given to regulatory networks involved in pituitary embryogenesis. Here, we give an overview of the current knowledge on the NOTCH, WNT, epithelial-mesenchymal transition, SHH and Hippo pathways in the pituitary stem/progenitor cell compartment during various (activation) conditions from embryonic over neonatal to adult age. Most information comes from expression analyses of molecular components belonging to these networks, whereas functional extrapolation is still very limited. From this overview, it emerges that the 'big five' embryonic pathways are indeed reiterated in the stem cells of the 'lazy' homeostatic postnatal pituitary, further magnified en route to activation in more energetic, physiological and pathological remodeling conditions. Increasing the knowledge on the molecular players that pull the regulatory strings of the pituitary stem cells will not only provide further fundamental insight in postnatal pituitary homeostasis and activation, but also clues toward the development of regenerative ideas for improving treatment of pituitary deficiency and tumors.

miR-7 mediates the signaling pathway of NE affecting FSH and LH synthesis in pig pituitary

“…The pituitary gland, a 'master gland' of the body, acts as a central endocrine regulator of growth (Brinkmeier et al 2009, Musumeci et al 2015, Cox et al 2017, reproduction (Brown & Roberson 2017), metabolism (Tanaka et al 2018) and the capacity to cope with stress (Aguilera 1994, Borrow et al 2019. The pituitary comprises the adenohypophysis (consisting of the anterior and intermediate lobes) and the neurohypophysis (posterior lobe) (Dubois & Elamraoui 1995, Kelberman et al 2009.…”

Stress-inducible-stem cells: a new view on endocrine, metabolic and mental disease?

“…An intricate network of morphogens and growth factors and a defined combinatorial code of transcription factors direct the hypothalamic, pituitary, and adrenal progenitor cells to form the mature HPA axis [29, 30]. External and internal stressors from the first day of life influence the process of cell differentiation of stem and progenitor cells in the HPA axis to form the fully functional endocrine stress system.…”

“…Major developmental signaling pathways are active in stem cells of the pituitary [30], and similar mechanism hold true for the peripheral effector organ of the HPA axis, the adrenal gland, in both the steroid-producing adrenal cortex and the catecholamine-producing adrenal medulla. This may suggest a uniform and coordinated signature and programming within the entire endocrine stress axis, thereby, hinting at common or shared pathways in generating stress-inducible stem cells (SISCs) shaping the entire adaptive stress response in the HPA axis and beyond.…”

Molecular Mechanisms of Pituitary Cell Plasticity

“…However, higher levels of purity are obtained with approaches that involve the expression of cell type-specific fluorescent proteins such as the enhanced green fluorescent protein (eGFP), linked to the gene promoter of a cell-type specific protein, such as somatotrope GH, enabled the use of fluorescent activated cell sorting technologies (FACS) that provide a pure population of live cells for downstream analyses ( 21 ). Development of pituitary cell-lineage tracing mouse models have identified a population of Sox2 -expressing stem cells in the adult pituitary that can differentiate to produce all hormone-expressing cell types ( 22 – 26 ). Although activation of this cell population has been observed under conditions of acute experimental stress, e.g., hormone cell type-specific cell oblation and organ loss, the extent to which this mechanism contributes to pituitary homeostasis and functional plasticity is unclear ( 27 ).…”