All higher life forms critically depend on hormones being rhythmically released by the anterior pituitary. The proper functioning of this gland is dynamically controlled by a complex set of regulatory mechanisms that ultimately determine the fine tuning of endocrine cells. Strikingly, the pituitary needs to retain its integrity in order secrete highly ordered hormone pulses (up to a thousand fold rise in hormone levels!) while it displays an apparently heterogeneous distribution of cells in histological (2-D) studies. It recently prompted us to re-evaluate the role of cell positioning in pituitary function. The production of GFP-tagged transgenic mice allowed us to visualise in 3-D entire endocrine cell populations within the pituitary parenchyma. Using 2-photon excitation microscopy to image the whole pituitary in GH-GFP transgenic mice, we identified a continuous 3-D network of growth hormone (GH) cells wiring the entire gland (Bonnefont et al., PNAS 102: 1688016885, 2005). The GH system exhibited the main three features of biological networks: robustness of GH network architecture across lifespan, modularity of cell positioning which varies with activity in the GH axis and body growth, and recurrent patterns of cell-cell connectivity in response to GHRH. Hence, these findings indicate that earlier 2-D histological studies missed the higher-level organizational properties of the pituitary. Pituitary-scale 3D cell imaging changes our view of GH cells, from a collection of dispersed cells to a geometrically connected homotypic network of cells. Preliminary data also showed large-scale network organization of other endocrine cell types (PRL, ACTH) suggesting that cell positioning and associated cell-cell connection mechanisms will be critical parameters that determine how well pituitary endocrine cell populations can deliver coordinated secretory pulses of hormones.
06 - 07 Nov 2006
Society for Endocrinology