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Immunometabolism (Cobham, Surrey) Jul 2023Nonalcoholic fatty liver disease (NAFLD) is a prevalent cause of liver disease and metabolic comorbidities. Obesity is strongly associated with NAFLD and is also a state... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) is a prevalent cause of liver disease and metabolic comorbidities. Obesity is strongly associated with NAFLD and is also a state of relative deficiency of growth hormone (GH). Evidence supports a role of reduced GH and insulin-like growth factor-1 (IGF-1) in NAFLD pathogenesis. Physiological actions of GH in the liver include suppression of de novo lipogenesis (DNL) and promotion of lipid beta-oxidation, and GH also appears to have anti-inflammatory actions. Physiologic actions of IGF-1 include suppression of inflammatory and fibrogenic pathways important in the evolution from steatosis to steatohepatitis and fibrosis. Rodent models of impaired hepatic GH signaling show the development of steatosis, sometimes accompanied by inflammation, hepatocellular damage, and fibrosis, and these changes are ameliorated by treatment with GH and/or IGF-1. In humans, individuals with GH deficiency and GH resistance demonstrate an increased prevalence of NAFLD compared to controls, with improvement in hepatic lipid, steatohepatitis, and fibrosis following GH replacement. As a corollary, individuals with GH excess demonstrate lower hepatic lipid compared to controls along with increased hepatic lipid following treatment to normalize GH levels. Clinical trials demonstrate that augmentation of GH reduces hepatic lipid content in individuals with NAFLD and may also ameliorate steatohepatitis and fibrosis. Taken together, evidence supports an important role for perturbations in the GH/IGF-1 axis as one of the pathogenic mechanisms of NAFLD and suggests that further study is needed to assess whether augmentation of GH and/or IGF-1 may be a safe and effective therapeutic strategy for NAFLD.
PubMed: 37520312
DOI: 10.1097/IN9.0000000000000030 -
Endocrine Journal Nov 2023Long-term stimulation of thyroid follicular epithelium by high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly can lead to...
Long-term stimulation of thyroid follicular epithelium by high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly can lead to thyroid dysfunction, goiter, thyroid nodules, and even thyroid cancer and thyroid-associated ophthalmopathy (TAO). Excessive GH/IGF-1 promotes goiter and thyroid nodule formation, which can be reversed by normalizing the IGF-1 levels with surgery or medical treatment. Whether patients with acromegaly have an increased risk of thyroid cancer remains controversial, and routine thyroid ultrasonography and regular cancer screening are recommended in such cases, especially when the nodules possess malignant propensity. TAO is an autoimmune disease and newer treatments are being discovered against it. Recent studies have reported that the IGF-1 receptor (IGF-1R) plays an important role in the pathogenesis of TAO, and the IGF-1R inhibitor teprotumumab involves significantly improved disease endpoints in patients with active TAO. Thyroid-stimulating hormone (TSH) receptor (TSHR) and IGF-1R co-immunoprecipitate in orbital and thyroid tissues to form a functional complex; thus, combined therapy targeting TSHR and IGF-1R may be more effective than single therapy.
Topics: Humans; Insulin-Like Growth Factor I; Acromegaly; Receptor, IGF Type 1; Thyroid Diseases; Graves Ophthalmopathy; Goiter; Receptors, Thyrotropin; Human Growth Hormone; Growth Hormone; Thyroid Neoplasms
PubMed: 37880078
DOI: 10.1507/endocrj.EJ23-0356 -
Frontiers in Endocrinology 2023The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway emerged in recent years as a key determinant of aging and longevity. Disruption of this... (Review)
Review
The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway emerged in recent years as a key determinant of aging and longevity. Disruption of this network in different animal species, including flies, nematodes and mouse, was consistently associated with an extended lifespan. Epidemiological analyses have shown that patients with Laron syndrome (LS), the best-characterized disease under the umbrella of the congenital IGF1 deficiencies, seem to be protected from cancer. While aging and cancer, as a rule, are considered diametrically opposite processes, modern lines of evidence reinforce the notion that aging and cancer might, as a matter of fact, be regarded as divergent manifestations of identical biochemical and cellular underlying processes. While the effect of individual mutations on lifespan and health span is very difficult to assess, genome-wide screenings identified a number of differentially represented aging- and longevity-associated genes in patients with LS. The present review summarizes recent data that emerged from comprehensive analyses of LS patients and portrays a number of previously unrecognized targets for GH-IGF1 action. Our article sheds light on complex aging and longevity processes, with a particular emphasis on the role of the GH-IGF1 network in these mechanisms.
Topics: Humans; Mice; Animals; Laron Syndrome; Aging; Longevity; Growth Hormone; Human Growth Hormone; Neoplasms
PubMed: 37941907
DOI: 10.3389/fendo.2023.1291812 -
Frontiers in Endocrinology 2024
Topics: Humans; Dwarfism; Human Growth Hormone
PubMed: 38606084
DOI: 10.3389/fendo.2024.1403112 -
International Journal of Molecular... Dec 2023Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in endocrine and non-endocrine tissues, immune cells and the central nervous system (CNS).... (Review)
Review
Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in endocrine and non-endocrine tissues, immune cells and the central nervous system (CNS). Post-release from secretory or immune cells, the first most appreciated role that SST exhibits is the antiproliferative effect in target tissue that served as a potential therapeutic intervention in various tumours of different origins. The SST-mediated in vivo and/or in vitro antiproliferative effect in the tumour is considered direct via activation of five different somatostatin receptor subtypes (SSTR1-5), which are well expressed in most tumours and often more than one receptor in a single cell. Second, the indirect effect is associated with the regulation of growth factors. SSTR subtypes are crucial in tumour diagnosis and prognosis. In this review, with the recent development of new SST analogues and receptor-specific agonists with emerging functional consequences of signaling pathways are promising therapeutic avenues in tumours of different origins that are discussed.
Topics: Humans; Receptors, Somatostatin; Somatostatin; Growth Hormone; Neoplasms; Biology
PubMed: 38203605
DOI: 10.3390/ijms25010436