Growth Hormone and Insulin-Like Growth Factor Dynamics in Liver Disease

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) form a critical endocrine axis governing hepatic growth, metabolism and repair. GH, produced by the anterior pituitary, binds to receptors on hepatocytes to stimulate IGF-1 synthesis, which then exerts paracrine and systemic actions on cell proliferation, lipid regulation and insulin sensitivity. In physiological states, GH promotes lipolysis and limits fat accumulation, while IGF-1 regulates activation of hepatic stellate cells and collagen deposition, maintaining extracellular matrix homeostasis. Disruption of this axis—through GH deficiency, receptor insensitivity or impaired IGF-1 signalling—predisposes to non-alcoholic fatty liver disease (NAFLD) and its inflammatory form, non-alcoholic steatohepatitis (NASH). Progressive inflammation, oxidative stress and stellate cell activation drive fibrosis, cirrhosis and hepatocellular carcinoma. Emerging interventions aim to restore GH–IGF-1 balance to reverse steatosis, attenuate fibrogenesis and improve insulin sensitivity, highlighting a promising route for addressing the global burden of chronic liver disease.

Research from Nature Portfolio

Seminal work has demonstrated that IGF-1 induces senescence in activated hepatic stellate cells via a p53-dependent pathway, thereby limiting fibrosis in models of NASH and cirrhosis. Administration of IGF-1 in experimental diets deficient in methionine–choline and in toxin-induced cirrhosis reduced steatosis, inflammation and collagen deposition. Mechanistic studies reveal that IGF-1 enhances mitochondrial function and reduces oxidative stress in the injured liver, positioning IGF-1 as a potential antifibrotic therapy.

Growth Hormone and Insulin-Like Growth Factor Dynamics in Liver Disease publication trend

The graph below shows the total number of articles in growth hormone and insulin-like growth factor dynamics in liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Growth Hormone (GH): A pituitary peptide hormone that stimulates growth, lipolysis and IGF-1 production.

Insulin-Like Growth Factor 1 (IGF-1): A liver-derived hormone mediating many downstream effects of GH on cells.

Non-Alcoholic Fatty Liver Disease (NAFLD): Excessive fat accumulation in the liver not caused by alcohol.

Non-Alcoholic Steatohepatitis (NASH): An inflammatory subtype of NAFLD characterised by hepatocyte injury and fibrosis.

Hepatic Stellate Cells (HSCs): Perisinusoidal liver cells that, when activated, secrete extracellular matrix proteins.

Fibrosis: The pathological accumulation of collagen leading to scar formation in liver tissue.

References

1. The Role of Growth Hormone and Insulin Growth Factor 1 in the Development of Non-Alcoholic Steato-Hepatitis: A Systematic Review. Cells (2023).
2. The Role of Growth Hormone and Insulin-Like Growth Factor-I in the Liver. International Journal of Molecular Sciences (2017).
3. IGF-I induces senescence of hepatic stellate cells and limits fibrosis in a p53-dependent manner. Scientific Reports (2016).
4. Liver-specific Deletion of the Growth Hormone Receptor Reveals Essential Role of Growth Hormone Signaling in Hepatic Lipid Metabolism* ♦. Journal of Biological Chemistry (2009).
5. Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD. Frontiers in Medicine (2021).
6. Insulin-like growth factor-1 attenuates oxidative stress-induced hepatocyte premature senescence in liver fibrogenesis via regulating nuclear p53–progerin interaction. Cell Death & Disease (2019).