Journal ArticleDOI
The growth hormone receptor: mechanism of activation and clinical implications
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TLDR
A model in which the growth hormone receptor exists as a constitutive dimer is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopOietin receptors.Abstract:
Growth hormone is widely used clinically to promote growth and anabolism and for other purposes. Its actions are mediated via the growth hormone receptor, both directly by tyrosine kinase activation and indirectly by induction of insulin-like growth factor 1 (IGF-1). Insensitivity to growth hormone (Laron syndrome) can result from mutations in the growth hormone receptor and can be treated with IGF-1. This treatment is, however, not fully effective owing to the loss of the direct actions of growth hormone and altered availability of exogenous IGF-1. Excessive activation of the growth hormone receptor by circulating growth hormone results in gigantism and acromegaly, whereas cell transformation and cancer can occur in response to autocrine activation of the receptor. Advances in understanding the mechanism of receptor activation have led to a model in which the growth hormone receptor exists as a constitutive dimer. Binding of the hormone realigns the subunits by rotation and closer apposition, resulting in juxtaposition of the catalytic domains of the associated tyrosine-protein kinase JAK2 below the cell membrane. This change results in activation of JAK2 by transphosphorylation, then phosphorylation of receptor tyrosines in the cytoplasmic domain, which enables binding of adaptor proteins, as well as direct phosphorylation of target proteins. This model is discussed in the light of salient information from closely related class 1 cytokine receptors, such as the erythropoietin, prolactin and thrombopoietin receptors.read more
Citations
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Journal ArticleDOI
Pegvisomant: a growth hormone receptor antagonist used in the treatment of acromegaly
TL;DR: Pegvisomant is an effective therapeutic agent in patients with acromegaly who are not in remission after undergoing pituitary surgery, and regular surveillance for possible tumor growth and adverse effects (hepatotoxicity, skin manifestations) is warranted.
Journal ArticleDOI
Defining human insulin-like growth factor I gene regulation.
TL;DR: In this paper, the authors investigated the role of growth hormone (GH) in the regulation of human IGF-I gene expression after generating cells in which the IGF1 chromosomal locus has been incorporated into a mouse cell line and found that GH rapidly stimulates human IGF1 gene transcription and identified several potential transcriptional enhancers in chromatin that bind STAT5b in a GH-regulated way.
Journal ArticleDOI
Downregulation of the Creatine Transporter SLC6A8 by JAK2
TL;DR: JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane.
OtherDOI
Impact of Growth Hormone on Regulation of Adipose Tissue.
Katie M. Troike,Brooke E. Henry,Elizabeth A. Jensen,Elizabeth A. Jensen,Jonathan A. Young,Jonathan A. Young,Edward O. List,John J. Kopchick,John J. Kopchick,Darlene E. Berryman,Darlene E. Berryman +10 more
TL;DR: The effects of GH on AT are numerous, dynamic and depot-dependent, and the efficacy of GH as a therapeutic option to manage obesity is given.
Journal ArticleDOI
Development and Characterization of a Novel Anti-idiotypic Monoclonal Antibody to Growth Hormone, Which Can Mimic Physiological Functions of Growth Hormone in Primary Porcine Hepatocytes
Hainan Lan,Hai-Long Jiang,Wei Li,Tian-Cheng Wu,Pan Hong,Yu Meng Li,H. Y. Zhang,Huan-Zhong Cui,Xin Zheng +8 more
TL;DR: This work indicates that a monoclonal anti-idiotypic antibody to GH (B-32) can serve as a GHR agonist or GH mimic and has application potential in domestic animal (pig) production.
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