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This version published online on July 1, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-0620
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Submitted on March 17, 2008
Accepted on June 23, 2008

Twenty-Four Hour Continuous Ghrelin Infusion Augments Physiologically Pulsatile, Nycthemeral and Entropic (Feedback-Regulated) Modes of GH Secretion

Johannes D. Veldhuis*, George Ann Reynolds, Ali Iranmanesh, and Cyril Y. Bowers

Endocrine Research Unit, Department of Internal Medicine, Clinical Translational Science Unit, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, MN 55905; Division of Endocrinology, Department of Internal Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112; Endocrine Section, Department of Medicine, Salem Veterans Affairs Medical Center, Salem, VA 24153

* To whom correspondence should be addressed. E-mail: veldhuis.johannes{at}mayo.edu.

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.

Location. Academic medical center.

Methods. Twenty-four h continuous sc infusion of saline vs ghrelin (1 µg/kg/h) with frequent sampling. Deconvolution and entropy analyses.

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

Results. Ghrelin 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 rose 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 fell 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 additive in driving GH secretion.

Conclusion. 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.


Key words: GH secretagogue • human • IGF-I







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