In the early 2000s, our lab began its efforts to characterize the large-scale functional organization of endocrine cell types within the mammalian pituitary gland. These studies were driven by a long-standing paradox of pituitary function: endocrine cell populations are capable of mounting massive hormone pulses in vivo (e.g. a 1,000-fold increase in GH levels in young mature males), while the same cells isolated from their tissue context respond weakly to secretagogue (two- and five-fold increase in GH levels in response to hypothalamic GHRH). Thus, we hypothesized that cell organization in situ might be a pivotal component in the build-up of hormone pulses. To address this paradox, we applied large-scale cellular microscopy to animal and more recently human pituitaries to examine the positioning and signaling activities of the embedded endocrine cell populations. In combination with other techniques (e.g. Ca2+-imaging, RNAseq and qPCR analyses…), we have been able to: 1) Show that mouse pituitary endocrine cells are organized as 3D networks, allowing the gland to integrate and memorize numerous external cues to appropriately adapt downstream tissue output to the prevailing environmental conditions; 2) Provide evidence that highly-organized networks of endocrine cells (at least somatotrophs and corticotrophs) also exist with the human pituitary parenchyma; 3) Identify a mode of cellcell communication within homotypic cell networks which may provide a useful diagnostic marker for staging aggressiveness in common human adenomas (GH and PRL); 4) Show that pituitary development involves inter-network communication; and 5) Identify how energy expenditure during the build-up of hormone pulses depends on paracrine interplay between endocrine cell networks and pituitary pericytes.
As such, the large-scale organization of endocrine cells into networks boosts pituitary hormone release by supporting complex cellcell information exchanges, and components of this may be targeted by pathological insults to perturb normal gland architecture and function.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology