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Evidence for Acyl-Ghrelin Modulation of Growth Hormone Release in the Fed State

Department of Medicine (R.N., L.S.F., J.L., S.S.P., M.C.O., B.D.G., M.O.T.), Division of Endocrinology and Metabolism, and Departments of Pharmacology (M.L.J., P.V.) and Chemistry (C.E.P., H.M.G.), University of Virginia, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Dr. Michael O. Thorner, Department of Medicine, University of Virginia, Box 801411, Charlottesville, Virginia 22908. E-mail: mot{at}virginia.edu.

Context: The timing and frequency of GH 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: The study was conducted at a university hospital general clinical research center.

Participants: Participants included eight men with mean (± SD) age 24.5 ± 3.7 yr (body mass index 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 when acyl-ghrelin levels declined [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/liter, P = 0.002; amplitude: 5.2 (1.3) vs. 11.8 (1.9) µg/liter/min, P = 0.034; pulses per 24 h: 19.4 (0.5) vs. 22.0 (1.4), P = 0.1].

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.