TY - JOUR
T1 - Twenty-four hour continuous Ghrelin infusion augments physiologically pulsatile, nycthemeral, and entropic (feedback-regulated) modes of growth hormone secretion
AU - Veldhuis, Johannes D.
AU - Reynolds, George Ann
AU - Iranmanesh, Ali
AU - Bowers, Cyril Y.
PY - 2008/9
Y1 - 2008/9
N2 - 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 μg/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 infusioncomparedwith saline infusion for 24h 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.
AB - 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 μg/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 infusioncomparedwith saline infusion for 24h 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.
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U2 - 10.1210/jc.2008-0620
DO - 10.1210/jc.2008-0620
M3 - Article
C2 - 18593763
AN - SCOPUS:51649097947
SN - 0021-972X
VL - 93
SP - 3597
EP - 3603
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -