Are Folliculo-Stellate Cells in the Anterior Pituitary Gland Supportive Cells or Organ-Specific Stem Cells?

Abstract

Folliculo-stellate cells (FS-cells) in the anterior pituitary gland are star-shaped cells and form tiny follicles. FS-cells are positive for S-100 protein and produce many cytokines or growth factors, such as interleukin-6 (IL-6), leukemia inhibitory factor (LIF), basic fibroblastic growth factor (bFGF) and vascular endothelial cell growth factor (VEGF). Therefore, it is generally accepted that FS-cells regulate endocrine cells through these growth factors. FS-cells also exhibit a phagocytotic activity and are known to work as scavenger cells. In addition to these functions, FS-cells are considered to have some unknown functions. In order to reveal the biological significance of FS-cells in the anterior pituitary gland, we performed a morphological study and obtained some new findings. First, we were interested in the colloid formation in the senescent porcine pituitary gland. We analyzed the colloids and found that clusterin is a major protein in them. We also found that the accumulation of clusterin in the colloids is related to the phagocytotic activity of FS-cells. In our next study, we found that FS-cells have the potential to differentiate into striated muscle cells. From FS-cells show multi-potent cell character and other cytological evidence, we propose that FS-cells are candidate of organ-specific stem cells in the anterior pituitary gland.

History and perspectives of pituitary folliculo-stellate cell research

“…Inoue and co-workers reported that skeletal muscle cells could differentiate from FS cells when a pituitary gland was transplanted under the kidney capsule (34). They confirmed this finding in vitro by showing the differentiation of Tpit/F1 cells into striated muscle cells (35).…”

“…A number of papers have recently provided evidence, although only circumstantially, for a role of FS cells as adult stem cells in the anterior pituitary (34,37). Horvath & Kovacs (37) demonstrated that in a large series of adenomatous and non-tumorous human pituitaries, immunoreactivities to S-100 and GFAP were strongest in newly formed follicles, the older microcysts being immunonegative.…”

“…At present, stem/progenitor cells are being found in a growing number of adult tissues, but have not been identified yet in the pituitary. FS cells have more than once been suggested to play a role as stem cells (34,37). Convincing evidence for a phenotypical change of FS cells into other pituitary cell types, however, is still to be provided.…”

“…In the Japanese school of F Yoshimura and coworkers, the idea that FS cells form a renewal cell system for endocrine cells, similar to the adult stem cell system of the brain (31,32), persisted from the late 60s (33) until the present day (34,35). Both the establishment of an immortalized FS cell-derived cell line (36), as well as the growing interest in transdifferentiation processes in the pituitary (35, 37 -39), have shed new light on these 'old' concepts.…”

Pituitary actions of ligands of the TGF-β family: activins and inhibins

“…The exact function of these S100 positive non-endocrine cells of the pituitary is not fully appreciated yet. They have been reported to be a major source of several paracrine factors of the pituitary to form a network that facilitates the synchronization of the pituitary gland or to represent a group of progenitor cells with the potential to differentiate into specialized endocrine cells (Allaerts et al 1990, Renner et al 1996, Stojilkovic 2001, Inoue et al 2002. Folliculostellate cell lines derived from rat, mouse, and human anterior pituitaries have been characterized in recent years and experiments with these cells are beginning to shed some light into the function of this cell type (Inoue et al 1992, Danila et al 2000b, Bilezikjian et al 2003.…”