Differential Regulation of Cholecystokinin Production by Synthetic and Natural Glucocorticoids in Enteroendocrine...

Chronic stress often causes abnormal eating behavior and metabolism due at least in part to the activation of hypothalamic-pituitary-adrenal (HPA) axis resulting in increases glucocorticoids secretion. Cholecystokinin (CCK) is an anorexic gut hormone secreted from enteroendocrine I cells and controls digestion through the gastric emptying and digestive enzyme secretion. In the present study, we highlighted the function of glucocorticoids in CCK-producing cells with enteroendocrine model cell lines and male Wistar rats. We found that glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are expressed in STC-1 cells known as an I cell model line. Synthetic (dexamethasone; DEX) and endogenous (corticosterone; CORT) glucocorticoids reduced CCK transcription in STC-1 cells. Depolarization-induced CCK secretion was attenuated by both glucocorticoids, whereas dietary peptide-induced CCK secretion was enhanced by acute CORT treatment. DEX and CORT treatments weakened phosphorylated signaling pathway for CCK transcription in an agonist-specific manner. Daily single injection of DEX but not CORT for 4 d decreased Cck mRNA in the upper small intestine with altered metabolism and gut glucocorticoid sensitivity in male Wistar rats. These findings provide a new insight to reveal stress-induced abnormal nutrient and metabolic status in relation to gastrointestinal dysfunctions.