title: 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.
authors.affiliation: Edison Biotechnology Institute, Ohio University, Athens, OH 45701, United States; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, United States. Electronic address: kopchick@ohio.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
authors.affiliation: Edison Biotechnology Institute, Ohio University, Athens, OH 45701, United States; Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, United States.
authors.forename: Edward O
authors.initials: EO
authors.lastname: List
authors.affiliation: Edison Biotechnology Institute, Ohio University, Athens, OH 45701, United States; Department of Pediatrics, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, United States.
authors.forename: Bruce
authors.initials: B
authors.lastname: Kelder
authors.affiliation: Edison Biotechnology Institute, Ohio University, Athens, OH 45701, United States.
authors.forename: Elahu S
authors.initials: ES
authors.lastname: Gosney
authors.affiliation: Edison Biotechnology Institute, Ohio University, Athens, OH 45701, United States; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, United States; School of Applied Health Sciences and Wellness, Ohio University, Athens, OH 45701, United States.
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Berryman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D013006:Growth Hormone / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D006727:Hormone Antagonists; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C406545:pegvisomant
keywords: FaGHRKO; GHA; GHR−/− mice; Growth hormone receptor antagonist (GHA); Pegvisomont; Somavert
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