Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly

Endocr Rev. 2002 Oct;23(5):623-46. doi: 10.1210/er.2001-0022.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acromegaly / drug therapy*
  • Animals
  • Clinical Trials as Topic
  • Drug Design
  • Human Growth Hormone / analogs & derivatives*
  • Human Growth Hormone / chemistry
  • Human Growth Hormone / genetics
  • Human Growth Hormone / physiology
  • Human Growth Hormone / therapeutic use
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Receptors, Somatotropin / analysis
  • Receptors, Somatotropin / antagonists & inhibitors*
  • Receptors, Somatotropin / genetics
  • Receptors, Somatotropin / physiology
  • Structure-Activity Relationship


  • Receptors, Somatotropin
  • Human Growth Hormone
  • pegvisomant