Glucocorticoids (GC) are steroid hormones produced by the adrenal glands under the control of the hypothalamic-pituitary-adrenal (HPA) axis. They regulate many physiological processes, including inflammation and metabolism. However, the action of GC on the enteric nervous system (ENS), a key player in digestive homeostasis, as well as their possible local production by the ENS, remain poorly understood.

We have recently demonstrated that the glucocorticoid receptor (GR) is expressed in enteric neurons, suggesting ENS sensitivity to GC. Indeed, treatment with corticosterone changes the phenotype of enteric neurons (Aubert et al., The FASEB Journal, 2019) and modifies their neuronal activity (Lowette et al., AJP Gastrointestinal and Liver Physiology, 2014). Furthermore, in a model of repeated acute stress, the acceleration of intestinal transit in mice is blocked by a GR inhibitor, reinforcing the involvement of GC in the modulation of intestinal functions controlled by the ENS (Blin et al., Frontiers in Neuroscience, 2023).

In addition to their adrenal production, local synthesis has been described in many tissues, particularly the intestine, where they play a central role in maintaining local homeostasis (Ahmed et al, Frontiers in Immunology, 2019). In the gastrointestinal tract, intestinal epithelial cells can synthesize GC, thereby influencing both the integrity of the intestinal epithelial barrier and the function of immune cells, particularly under inflammatory conditions. However, whether the ENS, a key regulator of intestinal function, can synthesize GC and how this synthesis might affect its function, particularly neuronal connectivity, remains unexplored.

Within the laboratory, we are therefore interested in (1) identifying more precisely the cell type contributing to local GC synthesis, (2) understanding the mechanisms regulating GC action in the ENS, and (3) understanding the functions of the ENS regulated locally by GC. A better understanding of these mechanisms could enable us to use this local GC production as a lever in digestive functional disorders.