Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (718 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A peptide of 44 amino acids in most species that stimulates the release and synthesis of growth hormone. GHRF (or GRF) is synthesized by neurons in the arcuate nucleus of the hypothalamus. After being released into the pituitary portal circulation, GHRF stimulates GH release by the somatotrophs in the pituitary gland.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Growth Hormone Releasing Hormone; GRF 1-44; Growth Hormone-Releasing Factor 44; Growth Hormone Releasing Factor 44; Somatotropin-Releasing Factor 44; Somatotropin Releasing Factor 44; Growth Hormone-Releasing Factor; Growth Hormone Releasing Factor.
Where it fits in the MeSH classification
- Broader topics
- Pituitary Hormone-Releasing Hormones
- Narrower topics
- Sermorelin
Related concepts
- Growth Hormone
- Arcuate Nucleus
- Hypothalamus
- Somatotrophs
- Pituitary Gland
Research landscape
PubMed indexes 5,219 records tagged with the MeSH heading “Growth Hormone-Releasing Hormone” (counts retrieved 2026-10-31). 208 of them (4.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 3,519 records.
Reviews account for 585 records (11.2%) and meta-analyses for 4. Randomized controlled trials number 254 (4.9%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 3,519 |
| 2000-2009 | 1,028 |
| 2010-2019 | 464 |
| 2020 onward | 208 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 585 | 11.2% |
| Meta-analyses | 4 | 0.1% |
| Randomized controlled trials | 254 | 4.9% |
Method: PubMed query "Growth Hormone-Releasing Hormone"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice | 2013 | Research article Design not recorded in structured metadata | 130 | cc by PMID 24175087 · DOI · PMC3810783 |
| Structural basis for activation of the growth hormone-releasing hormone receptor | 2020 | Research article Design not recorded in structured metadata | 79 | cc by PMID 33060564 · DOI · PMC7567103 |
| Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons | 2018 | Research article Design not recorded in structured metadata | 60 | cc by PMID 29795232 · DOI · PMC5966420 |
| Growth hormone-releasing hormone attenuates amyloid deposition and neuroinflammation in Alzheimer's disease models | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 41946684 · DOI · PMC13187343 |
Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice [1]
Abstract reading summary — source excerpts
- Opening excerpt
- We examine the impact of targeted disruption of growth hormone-releasing hormone (GHRH) in mice on longevity and the putative mechanisms of delayed aging.
- Closing excerpt
- 001.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
We examine the impact of targeted disruption of growth hormone-releasing hormone (GHRH) in mice on longevity and the putative mechanisms of delayed aging. GHRH knockout mice are remarkably long-lived, exhibiting major shifts in the expression of genes related to xenobiotic detoxification, stress resistance, and insulin signaling. These mutant mice also have increased adiponectin levels and alterations in glucose homeostasis consistent with the removal of the counter-insulin effects of growth hormone. While these effects overlap with those of caloric restriction, we show that the effects of caloric restriction (CR) and the GHRH mutation are additive, with lifespan of GHRH-KO mutants further increased by CR. We conclude that GHRH-KO mice feature perturbations in a network of signaling pathways related to stress resistance, metabolic control and inflammation, and therefore provide a new model that can be used to explore links between GHRH repression, downregulation of the somatotropic axis, and extended longevity. DOI:http://dx.doi.org/10.7554/eLife.01098.001.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 24175087 · DOI · PMC3810783
Structural basis for activation of the growth hormone-releasing hormone receptor [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR).
- Closing excerpt
- Our findings provide insights into the molecular basis of peptide recognition and receptor activation, thereby facilitating the development of structure-based drug discovery and precision medicine.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (186 words)
Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). Malfunction in GHRHR signaling is associated with abnormal growth, making GHRHR an attractive therapeutic target against dwarfism (e.g., isolated growth hormone deficiency, IGHD), gigantism, lipodystrophy and certain cancers. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein at 2.6 Å. This high-resolution structure reveals a characteristic hormone recognition pattern of GHRH by GHRHR, where the α-helical GHRH forms an extensive and continuous network of interactions involving all the extracellular loops (ECLs), all the transmembrane (TM) helices except TM4, and the extracellular domain (ECD) of GHRHR, especially the N-terminus of GHRH that engages a broad set of specific interactions with the receptor. Mutagenesis and molecular dynamics (MD) simulations uncover detailed mechanisms by which IGHD-causing mutations lead to the impairment of GHRHR function. Our findings provide insights into the molecular basis of peptide recognition and receptor activation, thereby facilitating the development of structure-based drug discovery and precision medicine.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33060564 · DOI · PMC7567103
Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Despite critical roles of the hypothalamic arcuate neurons in controlling the growth and energy homeostasis, the gene regulatory network directing their development remains unclear.
- Closing excerpt
- Together, our study demonstrates that the identity of GHRH- and AgRP-neurons is synchronously specified and segregated by the Dlx1/2-Otp gene regulatory axis.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (145 words)
Despite critical roles of the hypothalamic arcuate neurons in controlling the growth and energy homeostasis, the gene regulatory network directing their development remains unclear. Here we report that the transcription factors Dlx1/2 and Otp coordinate the balanced generation of the two functionally related neurons in the hypothalamic arcuate nucleus, GHRH-neurons promoting the growth and AgRP-neurons controlling the feeding and energy expenditure. Dlx1/2-deficient mice show a loss-of-GHRH-neurons and an increase of AgRP-neurons, and consistently develop dwarfism and consume less energy. These results indicate that Dlx1/2 are crucial for specifying the GHRH-neuronal identity and, simultaneously, for suppressing AgRP-neuronal fate. We further show that Otp is required for the generation of AgRP-neurons and that Dlx1/2 repress the expression of Otp by directly binding the Otp gene. Together, our study demonstrates that the identity of GHRH- and AgRP-neurons is synchronously specified and segregated by the Dlx1/2-Otp gene regulatory axis.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29795232 · DOI · PMC5966420
Growth hormone-releasing hormone attenuates amyloid deposition and neuroinflammation in Alzheimer's disease models [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau hyperphosphorylation, neuroinflammation, and synaptic loss.
- Closing excerpt
- Given their ability to modulate multiple pathological pathways, GHRH agonists may represent promising therapeutic candidates for AD and other neurodegenerative disorders.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (238 words)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, tau hyperphosphorylation, neuroinflammation, and synaptic loss. Existing therapies provide only modest symptomatic relief and fail to slow disease progression. Beyond its role in promoting pituitary growth hormone (GH) secretion, growth hormone-releasing hormone (GHRH) has shown neuroprotective effects in experimental ischemic stroke and spinal muscular atrophy. Here, we explored the therapeutic potential of GHRH and its agonist MR-409 in AD models. In vitro, GHRH(1-44)NH₂ promoted survival, proliferation, and neuronal differentiation of rat hippocampal neural stem cells (NSCs) and human SH-SY5Y neuroblastoma cells under growth factor deprivation and amyloid beta (Aβ)1-42 exposure. These effects involved the cAMP/PKA/CREB, ERK1/2, and PI3K/Akt signaling pathways. GHRH also attenuated Aβ-induced neurotoxicity by reducing apoptosis, suppressing GSK-3β activity and tau phosphorylation, restoring nuclear β-catenin, and inhibiting NF-κB-mediated inflammation. In vivo, subcutaneous administration of MR-409 in 5xFAD mice reduced Aβ deposition, tau phosphorylation, gliosis, and proinflammatory cytokine expression. In addition, MR-409 mitigated neuronal and synaptic loss, activated survival and neurogenic pathways, and improved cognitive performance, without altering systemic GH and IGF1 levels. MR-409 also elevated NRF2 mRNA expression while reducing its negative regulator KEAP1. Overall, these findings indicate that GHRH and its analog MR-409 exert neuroprotective effects by modulating key pathological features of AD, including neurodegeneration, impaired neurogenesis, neuroinflammation, and oxidative stress. Given their ability to modulate multiple pathological pathways, GHRH agonists may represent promising therapeutic candidates for AD and other neurodegenerative disorders.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41946684 · DOI · PMC13187343
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Growth hormone-releasing hormone [5]
- Research article Prader-Willi syndrome and the hypothalamus [6]
- Research article Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer [7]
- Research article Neurochemical regulation of sleep [8]
- Research article Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations [9]
- Research article Interrelations between sleep and the somatotropic axis [10]
References
- Sun LY, Spong A, Swindell WR, Fang Y, Hill C, Huber JA, et al.. Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. . 2013. PMID 24175087 · DOI · PMC3810783
- Zhou F, Zhang H, Cong Z, Zhao LH, Zhou Q, Mao C, et al.. Structural basis for activation of the growth hormone-releasing hormone receptor. . 2020. PMID 33060564 · DOI · PMC7567103
- Lee B, Kim J, An T, Kim S, Patel EM, Raber J, et al.. Dlx1/2 and Otp coordinate the production of hypothalamic GHRH- and AgRP-neurons. . 2018. PMID 29795232 · DOI · PMC5966420
- Pedrolli F, Morello G, Gesmundo I, Banfi D, Ferro A, Wangpaichitr M, et al.. Growth hormone-releasing hormone attenuates amyloid deposition and neuroinflammation in Alzheimer's disease models. . 2026. PMID 41946684 · DOI · PMC13187343
- Frohman LA, Jansson JO. Growth hormone-releasing hormone. Endocr Rev. 1986. PMID 2874984 · DOI
- Swaab DF. Prader-Willi syndrome and the hypothalamus. Acta Paediatr Suppl. 1997. PMID 9401539 · DOI
- Schally AV, Varga JL, Engel JB. Antagonists of growth-hormone-releasing hormone: an emerging new therapy for cancer. Nat Clin Pract Endocrinol Metab. 2008. PMID 18084344 · DOI
- Steiger A. Neurochemical regulation of sleep. J Psychiatr Res. 2007. PMID 16777143 · DOI
- Sano T, Asa SL, Kovacs K. Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations. Endocr Rev. 1988. PMID 3145190 · DOI
- Van Cauter E, Plat L, Copinschi G. Interrelations between sleep and the somatotropic axis. Sleep. 1998. PMID 9779515 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.