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Submitted on October 4, 2007
Accepted on March 3, 2008
Department of Medicine, Division of Endocrinology and Metabolism, Department of Pharmacology, Department of Chemistry, University of Virginia, Charlottesville, USA
* To whom correspondence should be addressed. E-mail: MOT{at}virginia.edu.
Context. The timing and frequency of growth hormone secretory episodes is regulated by GHRH and somatostatin. This study provides evidence for amplification of these GH pulses by endogenous acyl-ghrelin.
Design. Blood was sampled every 10 min for 26.5 h during a fed admission with standardized meals and also during the final 24 h of a 61.5 h fast. GH secretion profiles were derived from deconvolution of 10 min sampling data and full-length acyl-ghrelin levels were measured using a newly developed two-site sandwich assay.
Setting. University Hospital General Clinical Research Center.
Participants. Eight men: mean (±SD) age 24.5 ± 3.7 yr; BMI 24 ± 2.1 kg/m2.
Results. Correlations were computed between amplitudes of individual GH secretory events, and the average acyl-ghrelin concentration in the 60-min interval preceding each GH burst. In the fed state, the peak correlations were positive for all subjects and significantly higher than in the fasting state [mean(±SEM): 0.7(0.04) vs. 0.29(0.08), P =0.017]. In addition, long-term fasting was associated with an increase in the GH secretory pulse mass and amplitude but not frequency (fed vs. fasting pulse mass: 0.22(0.05) vs. 0.44(0.06) µg/L, P =0.002; amplitude: 5.2(1.3) vs. 11.8(1.9) µg/L/min, P =0.034; pulses per 24 h: 19.4(0.5) vs. 22.0(1.4), P =0.1). During long-term fasting, acyl-ghrelin levels declined and the correlation with GH observed in the fed state was no longer apparent.
Conclusion. Our data support the hypothesis that under normal conditions in subjects given regular meals endogenous acyl-ghrelin acts to increase the amplitude of GH pulses.
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