The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects
Open accessAbstract
The growth hormone receptor (GHR), although most well known for regulating growth, has many other important biological functions including regulating metabolism and controlling physiological processes related to the hepatobiliary, cardiovascular, renal, gastrointestinal, and reproductive systems. In addition, growth hormone signaling is an important regulator of aging and plays a significant role in cancer development. Growth hormone activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, and recent studies have provided a new understanding of the mechanism of JAK2 activation by growth hormone binding to its receptor. JAK2 activation is required for growth hormone-mediated activation of STAT1, STAT3, and STAT5, and the negative regulation of JAK-STAT signaling comprises an important step in the control of this signaling pathway. The GHR also activates the Src family kinase signaling pathway independent of JAK2. This review covers the molecular mechanisms of GHR activation and signal transduction as well as the physiological consequences of growth hormone signaling.
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Variants in genes governing MPS and hypertrophy influence muscle growth response to caloric surplus.
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Variability in GHR sensitivity and IGF-1 production contributes to differences in muscle gain.
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Individuals with GHR polymorphisms that enhance receptor activity experience more pronounced muscle growth in response to GH, as IGF-1 stimulates MPS and reduces protein degradation.
“Individuals with GHR polymorphisms that enhance receptor activity experience more pronounced muscle growth in response to GH, as IGF-1 stimulates MPS and reduces protein degradation [57].”
From Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management—A State-of-the-Art Narrative Review (2024) · cites this paper as [57]
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Long-Term Treatment of Growth Hormone Insensitivity Syndrome with IGF-I
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Variants in theGH-IGFaxis confer susceptibilityto lung cancerPreprint
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Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278 · see citing works
Pediatric obesity—Long‐term consequences and effect of weight loss
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- Authors
- Dehkhoda, F., Lee, C. M. M., Medina, J., & Brooks, A. J.
- Affiliations
- Translational Research Institute (AU)
- Corresponding author
- Brooks, Andrew J.
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-02-13
- Volume
- 9
- Pages
- 35-35
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC5816795
- OpenAlex
- W2790718366
- Cited by
- 304
- References
- 330
- Citations by year
- 2026: 37 · 2025: 41 · 2024: 33 · 2023: 46 · 2022: 46 · 2021: 50 · 2020: 35 · 2019: 13 · 2018: 3
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RUNE (Research UNE) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Health and Medical Research Council (APP1084797)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- growth hormone receptor, receptor activation, JAK/STAT signaling, JAK2 activation, STAT1, STAT3, STAT5, Src family kinases, signal transduction, growth hormone physiology, aging, cancer, metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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