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The Cholinergic System Controls Ghrelin Release and Ghrelin-Induced Growth Hormone Release in Humans

Department of Medicine III (C.M., P.N., A.L.), Clinical Division of Endocrinology and Metabolism; Department of Clinical Pharmacology (G.S., M.W.); and Ludwig Boltzmann Institute for Experimental Endocrinology (B.B., G.G., A.L.), Medical University of Vienna, 1090 Vienna, Austria

Address all correspondence and requests for reprints to: Christina Maier, M.D., Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail: christina.maier{at}akh-wien.ac.at.

The stomach-derived peptide hormone ghrelin induces appetite and GH release. Several ghrelin actions are possibly mediated and modulated by the central cholinergic system. The aim of this study was to investigate the influence of the unspecific cholinergic antagonist atropine and the acetylcholine esterase inhibitor pyridostigmine, a cholinergic enhancer on ghrelin plasma concentrations and ghrelin-induced GH release. We investigated plasma ghrelin concentrations, ghrelin-induced GH release, and glucose and insulin concentrations after administration of atropine or pyridostigmine, and ghrelin (in two different doses, 0.25 and 1 µg/kg body weight), alone and in combination in a randomized, double-blind, placebo-controlled, crossover study design on 12 young, healthy male volunteers.

Atropine alone significantly reduced fasting ghrelin levels by 25%, whereas under pyridostigmine alone ghrelin levels were unaltered. Ghrelin in combination with atropine induced significantly reduced GH concentrations compared with ghrelin administration alone for both ghrelin doses, whereas ghrelin-induced GH peak concentrations and areas under the curve were not enhanced by pyridostigmine treatment. These results suggest that, in humans, fasting ghrelin concentrations might be under cholinergic control and that the cholinergic system appears to modulate ghrelin-induced GH release.

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