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lüll Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly Kopchick JJ; Parkinson C; Stevens EC; Trainer PJEndocr Rev 2002[Oct]; 23 (5): 623-46An understanding of the events that occur during GH receptor (GHR) signaling has facilitated the development of a GHR antagonist (pegvisomant) for use in humans. This molecule has been designed to compete with native GH for the GHR and to prevent its proper or functional dimerization-a process that is critical for GH signal transduction and IGF-I synthesis and secretion. Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed. This review charts the discovery and development of GHR antagonists and details the experience gained in patients with acromegaly.|Acromegaly/*drug therapy[MESH]|Animals[MESH]|Clinical Trials as Topic[MESH]|Drug Design[MESH]|Human Growth Hormone/*analogs & derivatives/chemistry/genetics/physiology/therapeutic use[MESH]|Humans[MESH]|Models, Molecular[MESH]|Molecular Structure[MESH]|Receptors, Somatotropin/analysis/*antagonists & inhibitors/genetics/physiology[MESH]|Structure-Activity Relationship[MESH] |