Four-hour infusion of hydrocortisone does not suppress the nocturnal increase of circulating acyl- or desacyl-ghrelin concentrations in healthy young adults

J Clin Endocrinol Metab. 2014 Sep;99(9):E1696-700. doi: 10.1210/jc.2014-1210. Epub 2014 Jun 25.

Abstract

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 (3:00-7:00 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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Blood Glucose / metabolism
  • Circadian Rhythm / drug effects*
  • Ghrelin / blood*
  • Healthy Volunteers
  • Humans
  • Hydrocortisone / administration & dosage*
  • Hydrocortisone / blood
  • Infusions, Intravenous
  • Insulin / blood
  • Male
  • Sodium Chloride / administration & dosage
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Blood Glucose
  • Ghrelin
  • Insulin
  • ghrelin, des-n-octanoyl
  • Sodium Chloride
  • Adrenocorticotropic Hormone
  • Hydrocortisone