Anterior Pit cell networks (#16)
The importance of cell organisation in the regulation of hormone secretion has been shown for many endocrine tissues in studies where the response of dispersed, cultured cells to secretagogue stimulation depends on cell-cell contact. In addition, reaggregation of pituitary cells in certain conditions results in a similar pattern of cell organisation to that found in the intact gland, indicating neighbour recognition and encoding of cell sorting, differentiation and/or migration. Using a combination of sophisticated microscopy and transgenic animals with cell types identified with fluorescent markers, the organisation of pituitary cell types into homotypic networks becomes apparent. Ablation of cells of the somatotroph network has demonstrated the robustness of its organisation, as well as identified its reliance on GHRH. By combining fluorescent cell-identification with methods to monitor activity we have been able to show that organisation correlates with response to stimulation and that cells actively reorganize to modify gland output in different physiological states. Surprisingly, lactotroph cells, which have augmented organisation in response to the requirement for increased and sustained prolactin secretion during lactation, maintain a modified network in anticipation of future demand. Our recent studies seek to determine the importance of network organisation for cell communication over large distances, as well as their response to different patterns of stimulation. Several other important questions remain: what are the cellular factors mediating cell organisation and encoding both innate cell organisation, cell motility and reorganisation; how network organisation is maintained after cell renewal, in particular from undifferentiated precursors and pituitary stem cells; how interactions between networks affect pituitary function, in particular the role of a stem cell niche; and what roles networks have in pathology, particularly pituitary tumours?