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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Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development.
Kristina M. Mueller,Madeleine Themanns,Katrin Friedbichler,Jan-Wilhelm Kornfeld,Harald Esterbauer,Jan Tuckermann,Jan Tuckermann,Richard Moriggl +7 more
TL;DR: An overview of overlapping and distinct functions of hepatic GH-STAT5 and GC-GR signaling in growth/metabolism is provided and impaired STAT5 signaling sensitizes hepatocytes to injury and tumorigenic transformation is identified.
Journal ArticleDOI
Targeting growth hormone function: strategies and therapeutic applications.
TL;DR: Current and emerging strategies for antagonizing GH function and the potential disease indications are discussed, including strategies that either inhibit GH production, block its systemic receptor, or interrupt its downstream signaling pathways.
Journal ArticleDOI
Growth Hormone's Links to Cancer.
TL;DR: Replacement GH therapy in GH deficiency hypopituitary adults and short children has been shown to be safe when no other risk factors for malignancy are present, but the use of GH in cancer survivors and in short children with RASopathies, chromosomal breakage syndromes, or DNA-repair disorders should be carefully evaluated.
Journal ArticleDOI
Pentadecapeptide BPC 157 Enhances the Growth Hormone Receptor Expression in Tendon Fibroblasts
TL;DR: The BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormones and contribute to the healing of tendon.
Journal ArticleDOI
Growth hormone is permissive for neoplastic colon growth.
Vera Chesnokova,Svetlana Zonis,Cuiqi Zhou,Maria Victoria Recouvreux,Anat Ben-Shlomo,Takako Araki,Robert Barrett,Michael J. Workman,Kolja Wawrowsky,Vladimir A. Ljubimov,Magdalena Uhart,Shlomo Melmed +11 more
TL;DR: It is shown that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts, and proposed that GH is a molecular component of the “field change” milieu permissive for neoplastic colon growth.
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