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Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications.

Abstract
The discovery of a growth hormone receptor antagonist (GHA) was initially established via expression of mutated GH genes in transgenic mice. Following this discovery, development of the compound resulted in a drug termed pegvisomant, which has been approved for use in patients with acromegaly. Pegvisomant treatment in a dose dependent manner results in normalization of IGF-1 levels in most patients. Thus, it is a very efficacious and safe drug. Since the GH/IGF-1 axis has been implicated in the progression of several types of cancers, many have suggested the use of pegvisomant as an anti-cancer therapeutic. In this manuscript, we will review the use of mouse strains that possess elevated or depressed levels of GH action for unraveling many of GH actions. Additionally, we will describe experiments in which the GHA was discovered, review results of pegvisomant's preclinical and clinical trials, and provide data suggesting pegvisomant's therapeutic value in selected types of cancer.
AuthorsJohn J Kopchick, Edward O List, Bruce Kelder, Elahu S Gosney, Darlene E Berryman
JournalMolecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 386 Issue 1-2 Pg. 34-45 (Apr 5 2014) ISSN: 1872-8057 [Electronic] Ireland
PMID24035867 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Hormone Antagonists
  • Receptors, Somatotropin
  • pegvisomant
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Growth Hormone
Topics
  • Amino Acid Sequence
  • Animals
  • Growth Hormone (metabolism)
  • Hormone Antagonists (pharmacology, therapeutic use)
  • Human Growth Hormone (analogs & derivatives, chemistry, pharmacology, therapeutic use)
  • Insulin-Like Growth Factor I (metabolism)
  • Mice
  • Molecular Sequence Data
  • Neoplasms (drug therapy, metabolism, pathology)
  • Receptors, Somatotropin (antagonists & inhibitors, metabolism)

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