Special Issue "GH and GHR Signaling in Disease and Health"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling and Regulated Cell Death".

Deadline for manuscript submissions: 10 July 2021.

Special Issue Editor

Dr. Vera M. Chesnokova
E-Mail Website
Guest Editor
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States
Interests: GH; DNA damage; cellular senescence; aging; cancer

Special Issue Information

Dear Colleagues,

Research on the effects of growth hormone (GH) on physiologic processes is generating much debate and controversy. Accumulating evidence supports the direct effects of GH on multiple cell types and tissues, independent of its systemic actions via the GH/IGF1 axis. GH is involved in bone, muscle, and adipose tissue homeostasis, as well as glucose metabolism.

The remarkable longevity and increased healthspan in animal models with GH signaling deficiency, and its protective effects in human patients with GHR mutation against cancer, diabetes, and atherosclerosis have led some to hypothesize that somatopause, or age-related decline in secreted GH, is an evolutionary mechanism defending from age-associated diseases. Based on these observations, GH-related products are being widely marketed as anti-aging therapy and enhancers of athletic performance. However, GH excess alters DNA damage repair, and many animal models with GH overexpression develop neoplasia and have a shorter life span. In cancers, GH excess modifies the tumor microenvironment, promoting chemo- and radiotherapy resistance. These findings highlight potentially adverse risks for GH administration in pituitary-replete adults.

These contrary findings undoubtedly reflect the large variety of molecular and cellular processes affected by GH. A better understanding of the molecular mechanisms driving GH action, as well as elucidation of involved pathways, is critically needed.

This Special Issue is a forum that will bring together a collection of original research articles, reviews, and communications covering any topics related to GH actions, and/or its physiological/pathophysiological roles.

Dr. Vera M. Chesnokova
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • GH
  • GHR
  • animal models
  • tumorigenesis
  • metabolic pathways
  • GH signaling mutations
  • age-related pathologies
  • anti-aging therapy
  • longevity
  • somatopause

Published Papers (3 papers)

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Review

Open AccessReview
Central Regulation of Metabolism by Growth Hormone
Cells 2021, 10(1), 129; https://doi.org/10.3390/cells10010129 - 11 Jan 2021
Cited by 1 | Viewed by 659
Abstract
Growth hormone (GH) is secreted by the pituitary gland, and in addition to its classical functions of regulating height, protein synthesis, tissue growth, and cell proliferation, GH exerts profound effects on metabolism. In this regard, GH stimulates lipolysis in white adipose tissue and [...] Read more.
Growth hormone (GH) is secreted by the pituitary gland, and in addition to its classical functions of regulating height, protein synthesis, tissue growth, and cell proliferation, GH exerts profound effects on metabolism. In this regard, GH stimulates lipolysis in white adipose tissue and antagonizes insulin’s effects on glycemic control. During the last decade, a wide distribution of GH-responsive neurons were identified in numerous brain areas, especially in hypothalamic nuclei, that control metabolism. The specific role of GH action in different neuronal populations is now starting to be uncovered, and so far, it indicates that the brain is an important target of GH for the regulation of food intake, energy expenditure, and glycemia and neuroendocrine changes, particularly in response to different forms of metabolic stress such as glucoprivation, food restriction, and physical exercise. The objective of the present review is to summarize the current knowledge about the potential role of GH action in the brain for the regulation of different metabolic aspects. The findings gathered here allow us to suggest that GH represents a hormonal factor that conveys homeostatic information to the brain to produce metabolic adjustments in order to promote energy homeostasis. Full article
(This article belongs to the Special Issue GH and GHR Signaling in Disease and Health)
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Open AccessReview
Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation
Cells 2020, 9(11), 2446; https://doi.org/10.3390/cells9112446 - 09 Nov 2020
Cited by 1 | Viewed by 535
Abstract
Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor (GH-R) gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth [...] Read more.
Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor (GH-R) gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies. Epidemiological analyses have shown that LS patients do not develop cancer, whereas heterozygous family members have a cancer prevalence similar to the general population. To identify genes and signaling pathways differentially represented in LS that may help delineate a biochemical and molecular basis for cancer protection, we have recently conducted a genome-wide profiling of LS patients. Studies were based on our collection of Epstein–Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from LS patients, relatives and healthy controls. Bioinformatic analyses identified differences in gene expression in several pathways, including apoptosis, metabolic control, cytokine biology, Jak-STAT and PI3K-AKT signaling, etc. Genes involved in the control of cell cycle, motility, growth and oncogenic transformation are, in general, down-regulated in LS. These genetic events seem to have a major impact on the biological properties of LS cells, including proliferation, apoptosis, response to oxidative stress, etc. Furthermore, genomic analyses allowed us to identify novel IGF1 downstream target genes that have not been previously linked to the IGF1 signaling pathway. In summary, by ‘mining’ genomic data from LS patients, we were able to generate clinically-relevant information in oncology and, potentially, related disciplines. Full article
(This article belongs to the Special Issue GH and GHR Signaling in Disease and Health)
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Open AccessReview
Growth Hormone-Releasing Hormone in Lung Physiology and Pulmonary Disease
Cells 2020, 9(10), 2331; https://doi.org/10.3390/cells9102331 - 21 Oct 2020
Cited by 1 | Viewed by 643
Abstract
Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 [...] Read more.
Growth hormone-releasing hormone (GHRH) is secreted primarily from the hypothalamus, but other tissues, including the lungs, produce it locally. GHRH stimulates the release and secretion of growth hormone (GH) by the pituitary and regulates the production of GH and hepatic insulin-like growth factor-1 (IGF-1). Pituitary-type GHRH-receptors (GHRH-R) are expressed in human lungs, indicating that GHRH or GH could participate in lung development, growth, and repair. GHRH-R antagonists (i.e., synthetic peptides), which we have tested in various models, exert growth-inhibitory effects in lung cancer cells in vitro and in vivo in addition to having anti-inflammatory, anti-oxidative, and pro-apoptotic effects. One antagonist of the GHRH-R used in recent studies reviewed here, MIA-602, lessens both inflammation and fibrosis in a mouse model of bleomycin lung injury. GHRH and its peptide agonists regulate the proliferation of fibroblasts through the modulation of extracellular signal-regulated kinase (ERK) and Akt pathways. In addition to downregulating GH and IGF-1, GHRH-R antagonist MIA-602 inhibits signaling pathways relevant to inflammation, including p21-activated kinase 1-signal transducer and activator of transcription 3/nuclear factor-kappa B (PAK1-STAT3/NF-κB and ERK). MIA-602 induces fibroblast apoptosis in a dose-dependent manner, which is an effect that is likely important in antifibrotic actions. Taken together, the novel data reviewed here show that GHRH is an important peptide that participates in lung homeostasis, inflammation, wound healing, and cancer; and GHRH-R antagonists may have therapeutic potential in lung diseases. Full article
(This article belongs to the Special Issue GH and GHR Signaling in Disease and Health)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. Title: Regulation of GH and GH signaling by nutrients

Authors: Marina Caputo; Emanuela Agosti; Flavia Prodam

Affiliation: Department of Health Sciences, University of Piemonte Orientale, Novara, Italy

2. Title: IGF/GH axis in dento-alveolar complex: from development to aging and therapeutics

Authors: Kouassi Armel Koffi; Sophie Doublier; Jean-Marc Ricort; Sylvie Babajko; Juliane Isaac

Affiliation: Centre de Recherche des Cordeliers, INSERM, Université de Paris, Sorbonne-Université, 15 rue de l’école de médecine, Paris, France

3. Title: Direct and Indirect Actions of GH in Controlling Hepatic Lipid Accumulation
Authors: Rhonda D Kineman; Maria del Carmen Vazquez Borrego; Mercedes Del Rio Morenoet
Affiliation: Jesse Brown VA Medical Center, Research and Development Division, University of Illinois College of Medicine

4. Title: Dynamic regulation of GH-IGF-1 signaling in injury and recovery in hyperoxia-induced neonatal lung injury
Authors: Jasmine Mohr; Christina Vohlen; Alexey Fomenko; Tiffany Grzembke; Rebecca Wilke; Jörg Dötsch; Miguel A. Alejandre-Alcazar
Affiliation: University Hospital Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne Excellence Cluster for Stress Responses in Ageing-associated diseases (CECAD), Institut for Lung Health (ILH) Universities of Gießen and Marburg Lung Center (UGMLC), German Center for Lung Research, German

5. Topic: Review on the Hypothalamic GHR-SIRT1 Axis in Aging
Authors: Marianna Sadagurski; Juliana Lima
Affiliation: Department of Biological Sciences, IBio (Integrative Biosciences Center), Wayne State University, Detroit, MI 48202, USA

6. Title: Hormonal signals from the pituitary gland related to running performance in mice
Authors: Christina Walz; Julia Brenmoehl; Andreas Hoeflich
Affiliation: Leibniz Institute for Farm Animal Biology (FBN) Dummerstorf, Germany

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