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Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly

Edison Biotechnology Institute (J.J.K., E.C.S.), Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio, 45701; and Christie Hospital (C.P., P.J.T.), Department of Endocrinology, Manchester, M20 4BX, United Kingdom

Correspondence: Address all correspondence and requests for reprints to: Dr. P. J. Trainer, Department of Endocrinology, Christie Hospital, Manchester, M20 4BX, United Kingdom. E-mail: Peter.Trainer{at}man.ac.uk

An 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.

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