Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans

Objectives: Ghrelin is produced and secreted by the stomach promoting appetite and food intake and was identified as an endogenous ligand for the growth hormone secretagogue-receptor. A gastro-hypophyseal feedback loop seems to regulate gastric ghrelin secretion transducing changes in food intake to CNS in order to regulate energy homeostasis. The activity of ghrelin also includes stimulatory effects on the corticotropic system. However, little is known about the influence of glucocorticoids on ghrelin levels. The aim of our study was to investigate ghrelin levels with and without elevated glucocorticoid levels from either endogenous or exogenous origin. Methods: Plasma ghrelin levels were measured in five patients with chronic hypercortisolism (aged 29 to 58, median 46 years) due to Cushing syndrome before and after successful surgery of adenoma, and in eight healthy controls (aged 24 tom 39, median 27.5 years) before and after 30mg prednisolone (for five days) once a day in the morning (median BMI 22.7kg/m 2 ). Plasma ghrelin levels were measured by a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA). Results: In patients plasma ghrelin levels (median 363.2 pg/ml, range 161.9 to 525.7 pg/ml) significantly increased after successful surgery by 26.6% (P=0.04) while BMI decreased (median: from 26.2kg/m 2 to 24.0kg/m 2 , P=0.04). Both parameters were inversely correlated (r=-0.9, P=0.04). In healthy controls, plasma ghrelin levels (median 288.7 pg/ml, range 119.6 to 827.8 pg/ml) significantly decreased by 18.3% (P=0.04) after prednisolone treatment. Conclusions: We show for the first time that plasma ghrelin levels are decreased under endogenous or exogenous induced hypercortisolism. Ghrelin seems to be regulated by a negative feedback concerning the hypothalamic-pituitary-adrenal axis and might be involved in the pathogenesis of steroid induced obesity.