Endocrine Abstracts

Pituitary folliculostellate (FS) cells were originally described in 1953 and comprise up to 10% of the anterior pituitary cell population. These epithelioid cells are thought to be derived from neuroectodermal cells and express S-100, a nervous tissue-selective protein that is used to define FS phenotype. Unlike their endocrine counterparts, they are devoid of secretory granules and were considered non-secretory until relatively recently. Experiments using pituitary slices have demonstrated that FS cells are organised structurally into three-dimensional networks capable of intercellular communication via gap junction-mediated calcium wave propagation. Our understanding of the functional relevance of these cells has been greatly advanced with the advent of FS cell lines, two of which are in widespread use (TtT/GF and Tpit/F1). Studies using these cell lines have demonstrated a role for FS cells in three broad areas of pituitary function: autocrine/paracrine regulation of anterior pituitary cell function via cytokines and growth factors, intrapituitary communication between various cell types, and modulation of inflammatory responses. The concept of FS cells as key mediators in the neuro-immune/endocrine regulation of inflammation is gaining credence and is supported by evidence on several levels including expression of components of the innate immune system (C3a, C5a receptors), secretion of inflammatory cytokines (IL-6 and MIF) and regulation of these cytokines by anti-inflammatory molecules (including glucocorticoids and adenosine). Global gene expression profiling lends further support to these observations with the demonstration of Nur77, endothelial protein C receptor and thrombomodulin induction by adenosine agonists in TtT/GF cells. However, recent observations suggest that pituitary FS cells are not a homogeneous population but comprise subsets of cells with different immunophenotypes, though it is unclear whether these populations are truly distinct or merely represent cells at differing stages of development. Intriguingly, transdifferentiation experiments raise the possibility that FS cells could also represent a pituitary stem cell population.