Pegvisomant is a genetically manipulated growth hormone (GH) that disables signal transduction through the GH receptor and thus functions as a GH receptor antagonist. In a series of studies of the metabolic effects of GH in healthy male individuals, pegvisomant has been used to create a model of acute GH deficiency but without the typical alterations in body composition. This review summarizes studies of the effects of GH receptor blockade and fasting, either alone or in combination, on determinants of GH release. Based on these and other data we present a model to explain the somatotroph hyperactivity of fasting
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