Twenty-four hour continuous ghrelin infusion augments physiologically pulsatile, nycthemeral, and entropic (feedback-regulated) modes of growth hormone secretion

J Clin Endocrinol Metab. 2008 Sep;93(9):3597-603. doi: 10.1210/jc.2008-0620. Epub 2008 Jul 1.


Background: Ghrelin is a 28-amino acid acylated peptide that potentiates GHRH stimulation and opposes somatostatin inhibition acutely. Whether prolonged ghrelin administration can sustain physiological patterns of GH secretion remains unknown.

Hypothesis: Continuous delivery of ghrelin will amplify physiological patterns of GH secretion over 24 h.

Subjects: Men and women ages 29-69 yr, body mass indices 23-52 kg/m2, were included in the study.

Location: The study was performed at an academic medical center.

Methods: Twenty-four hour continuous sc infusion of saline vs. ghrelin (1 microg/kg.h) with frequent sampling was examined. Deconvolution and entropy analyses were performed.

Outcomes: IGF-I concentrations were determined. Basal, pulsatile, nycthemeral, and entropic measures of GH secretion were calculated.

Results: Ghrelin infusion compared with saline infusion for 24 h elevated (median) acylated ghrelin, GH, and IGF-I concentrations by 8.1-fold (P < 0.001),11-fold (P < 0.001), and 1.4-fold (P = 0.002). GH secretory-burst mass and frequency increased by 6.6-fold (P = 0.004) and 1.7-fold (P < 0.001), respectively, resulting in a 12-fold increase in pulsatile GH secretion (P < 0.001). Interpulse variability decreased significantly (P = 0.046), whereas GH secretory-burst shape and half-life did not change. The amplitude of the nycthemeral GH rhythm increased by 3.4-fold (P < 0.001), and GH patterns became more irregular (higher approximate entropy P < 0.001). Combining GHRH with ghrelin was not an additive in driving GH secretion.

Conclusions: Continuous ghrelin infusion for 24 h elevates acylated ghrelin, GH and IGF-I concentrations, and stimulates pulsatile, nycthemeral, and entropic modes of GH secretion. The consistency of outcomes in a heterogeneous cohort of adults suggests potentially broad utility of this physiological secretagogue in hyposomatotropic states.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Circadian Rhythm / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Feedback, Physiological / drug effects*
  • Female
  • Ghrelin / administration & dosage*
  • Growth Hormone-Releasing Hormone / administration & dosage
  • Human Growth Hormone / blood
  • Human Growth Hormone / metabolism*
  • Humans
  • Infusion Pumps
  • Insulin-Like Growth Factor I / analysis
  • Male
  • Middle Aged
  • Pulsatile Flow / drug effects*
  • Time Factors


  • Ghrelin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Growth Hormone-Releasing Hormone