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


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


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


METHODS
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.


RESULTS
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.
Veldhuis
Johannes D
JD
Endocrine Research Unit, Department of Internal Medicine, Clinical Translational Science Unit, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Reynolds
George Ann
GA
Iranmanesh
Ali
A
Bowers
Cyril Y
CY
D000328:Adult; D000368:Aged; D002940:Circadian Rhythm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D025461:Feedback, Physiological / Q000187:drug effects*; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007260:Infusion Pumps; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011673:Pulsatile Flow / Q000187:drug effects*; D013997:Time Factors
D054439:Ghrelin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone