Four-Hour Infusion of Hydrocortisone Does Not Suppress the Nocturnal Increase of Circulating Acyl- or Desacyl-Ghrelin Concentrations in Healthy Young Adults

Background: Ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin is found in the circulation in two forms: acyl-and desacyl-ghrelin. Acyl- and desacyl-ghrelin concentrations increase at night, when cortisol concentrations are low. Acute ghrelin administration increases ACTH and cortisol concentrations and a feedback loop between the ghrelin and ACTH-cortisol axis has been postulated. A previous study showed that exogenously induced hypercortisolism for 5 days decreased plasma ghrelin concentrations. Objective: The objective of the study was to determine whether a 4-hour infusion of hydrocortisone given at a time of low endogenous cortisol concentrations (11:00 PM to 3:00 AM) acutely suppresses acyl- and desacyl-ghrelin. Methods: Eight healthy young men aged (mean +/- SD) 21.5 +/- 2.7 years with a body mass index of 22.4 +/- 2.5 kg/m(2) were studied in a single-blind, placebo-controlled study during two separate overnight admissions on the Clinical Research Unit. The volunteers received either a 4-hour (11:00 PM to 3:00 AM) infusion of hydrocortisone or a saline infusion. The hydrocortisone infusion rate was 0.3 mg/kg.h for the initial 3 minutes, 0.24 mg/kg.h for 9 minutes, and then 0.135 mg/kg.h until the end of the infusion. Plasma acyl- and desacyl-ghrelin concentrations (in-house two site sandwich assay) and ACTH, cortisol, insulin, GH, and glucose levels were measured every 10 minutes for 16 hours (5:00 PM to 9:00 AM). Results: The mean differences (lower 95% limit; upper 95% limit) between the saline infusion and hydrocortisone infusion for acyl-and desacyl-ghrelin concentrations were not significantly different from zero. The infusion period (11:00 PM to 3:00 AM) was as follows: acyl-ghrelin, 0.22 (-7.39; 7.83) (P = 1.00); desacyl-ghrelin, -3.36 (-17.66; 10.95) (P = 1.00). The postinfusion period (3: 007: 00 AM) was as follows: acyl-ghrelin, 8.68 (1.07; 16.28); (P = .056); desacyl-ghrelin, 8.75 (-5.56; 23.05) (P = .403). Conclusions: A short-term increase in circulating cortisol concentrations by exogenous hydrocortisone infusion does not suppress circulating nocturnal acyl-or desacyl-ghrelin concentrations. Thus, it is likely that the diurnal pattern of ghrelin secretion is under circadian control and not directly regulated by cortisol.