TY - JOUR
T1 - Evaluation of growth hormone (GH) action in mice
T2 - Discovery of GH receptor antagonists and clinical indications
AU - Kopchick, John J.
AU - List, Edward O.
AU - Kelder, Bruce
AU - Gosney, Elahu S.
AU - Berryman, Darlene E.
PY - 2014/4/5
Y1 - 2014/4/5
N2 - 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.
AB - 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.
KW - FaGHRKO
KW - GHA
KW - GHR-/- mice
KW - Growth hormone receptor antagonist (GHA)
KW - Pegvisomont
KW - Somavert
UR - http://www.scopus.com/inward/record.url?scp=84896726383&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2013.09.004
DO - 10.1016/j.mce.2013.09.004
M3 - Review
C2 - 24035867
AN - SCOPUS:84896726383
SN - 0303-7207
VL - 386
SP - 34
EP - 45
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -
