Role of folliculo-stellate cells in the anterior pituitary: a historical review
Cell developmental studies have frequently used the hypophysis as a model for complex differentiation pathways. Nevertheless, many of this work has been focused on the hormone-producing cell types of the anterior pituitary (AP), whereas the so-called folliculo-stellate cells (FS cells) have often been ignored in these studies. FS cells form an enigmatic, non-hormone-secreting cell group. Initially designated as supportive cells, they were soon found to be the putative source of many, newly discovered peptides and growth factors. They were also shown to be involved in paracrine communication with other pituitary cell types and in communication through electrically coupled syncytia. Moreover, several authors have provided evidence for their possible role in pituitary cell regeneration and processes of cell transdifferentiation.
So far, little is known about the precise embryological origin of the mature FS cells. Since the discovery of adult stem cell populations in various organs, several authors have indicated a possible role of FS cells in this respect too. Also new evidence relating FS cells to the production of cytokines, their involvement in nitric oxide signaling and an in vitro immune accessory function were added to the list of physiological roles of the FS cells. The question however is whether these multiple functions can be ascribed to one, homogeneous but pluripotent cell type, or whether the pituitary FS cells represent a heterogeneous cell group consisting of various subtypes (unrelated or related to a common ancestor cell type).
We previously demonstrated the partial overlap between immunocompetent MHC-class II-positive dendritic cells (DC) and S100 protein-positive FS cells. In a transgenic mouse model for conditional DC ablation, we showed that early macrophages could be prevented from colonizing the AP. Also, around embryonic day 12 of chick development, early macrophages were detected in the anterior pituitary before pituitary cell differentiation was completed and well before FS cells obtained their mature phenotype.
The present historical review of FS cell research highlights the importance of conceptual frameworks in cell lineage studies. Cell biological systems from the past, like the reticulo-endothelial system or the more recent mononuclear phagocyte system, nowadays are considered obsolete and incomplete. Still there is a need for theoretical frameworks in new annotation studies and for the clinical applications of contemporary research. The FS cell model not only is very interesting for the study of development of organs with two or more embryonic Anlagen. Also, questions related to the therapeutic usefulness of pituitary cell regeneration are envisaged in cases of pituitary dysfunctioning or hypopituitarism.