GH Receptor Antagonist Therapy

GH binds to its hepatic receptors, inducing dimerization, which signals a cascade of molecular events culminating in IGF-1 generation (114). Pegvisomant, a genetically engineered GH analog, binds to the GH receptor (Fig. 9) and prevents functional GH receptor dimerization, thereby preventing GH signal transduction and subsequent IGF-1 generation (115-117). This novel mechanism of action inhibits peripheral GH action, rather than decreasing GH secretion. Pegvisomant administered by daily subcutaneous injection normalizes IGF-1 levels in more than 90% of patients, with decreased fatigue, soft tissue swelling and perspiration (117). Pegvisomant has not yet been approved by the Food and Drug Administration.

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