title: Revealing the large-scale network organization of growth hormone-secreting cells.
abstract: Pituitary growth hormone (GH)-secreting cells regulate growth and metabolism in animals and humans. To secrete highly ordered GH pulses (up to 1,000-fold rise in hormone levels in vivo), the pituitary GH cell population needs to mount coordinated responses to GH secretagogues, yet GH cells display an apparently heterogeneous scattered distribution in 2D histological studies. To address this paradox, we analyzed in 3D both positioning and signaling of GH cells using reconstructive, two-photon excitation microscopy to image the entire pituitary in GH-EGFP transgenic mice. Our results unveiled a homologous continuum of GH cells connected by adherens junctions that wired the whole gland and exhibited the three primary features of biological networks: robustness of architecture across lifespan, modularity correlated with pituitary GH contents and body growth, and connectivity with spatially stereotyped motifs of cell synchronization coordinating cell activity. These findings change our view of GH cells, from a collection of dispersed cells to a geometrically connected homotypic network of cells whose local morphology and connectivity can vary, to alter the timing of cellular responses to promote more coordinated pulsatile secretion. This large-scale 3D view of cell functioning provides a powerful approach to identify and understand other networks of endocrine cells that are thought to be scattered in situ. Many dispersed endocrine systems exhibit pulsatile outputs. We suggest that cell positioning and associated cell-cell connection mechanisms will be critical parameters that determine how well such systems can deliver a coordinated secretory pulse of hormone to their target tissues.
authors.affiliation: Department of Endocrinology, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale U661, Universities of Montpellier 1 and 2, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Bonnefont
authors.forename: Alain
authors.initials: A
authors.lastname: Lacampagne
authors.forename: Angela
authors.initials: A
authors.lastname: Sanchez-Hormigo
authors.forename: Elodie
authors.initials: E
authors.lastname: Fino
authors.forename: Audrey
authors.initials: A
authors.lastname: Creff
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Mathieu
authors.forename: Sébastien
authors.initials: S
authors.lastname: Smallwood
authors.forename: Danielle
authors.initials: D
authors.lastname: Carmignac
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontanaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Travo
authors.forename: Gérard
authors.initials: G
authors.lastname: Alonso
authors.forename: Nathalie
authors.initials: N
authors.lastname: Courtois-Coutry
authors.forename: Steve M
authors.initials: SM
authors.lastname: Pincus
authors.forename: Iain C A F
authors.initials: IC
authors.lastname: Robinson
authors.forename: Patrice
authors.initials: P
authors.lastname: Mollard
mesh_terms: D000818:Animals; D013006:Growth Hormone / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*
chemical_list: D013006:Growth Hormone