GHRP-6 Peptide
Growth hormone–releasing hexapeptide (GHRP-6) is a synthetic peptide developed for its potential to stimulate and modulate growth hormone secretion. Like many compounds in this class, it is an analog of the endogenous peptide met-enkephalin, but it is described as lacking typical opioid activity. Instead, GHRP-6 engages growth hormone secretagogue receptors (GHS-Rs), later identified as ghrelin receptors, so it is commonly referred to as a growth hormone secretagogue. It is a small, low–molecular weight peptide studied for possible GH-stimulating effects.
GHRPs were originally created to mimic aspects of growth hormone–releasing hormone (GHRH) biology yet act through a distinct pathway, showing affinity for ghrelin receptors. Because ghrelin is produced by the stomach during fasting, researchers have proposed that GHRPs, like ghrelin, may act through hypothalamic signaling and could influence functions linked to metabolism and nutrient handling.
Overview
Research has examined whether GHRP-6 requires endogenous GHRH to exert its effects. In one study using a GHRH antagonist versus saline, serial blood sampling indicated lower GH levels when the antagonist was present, suggesting that native GHRH may be necessary for the full action of GHRP-6.
Although the precise mechanism remains under investigation, reports suggest GHRPs may signal through two receptors, GHS-R1a and CD36. Beyond GH release, GHRP-6 has been noted for potential cytoprotective activity via CD36, possibly engaging pro-survival pathways.
A separate experiment explored a dual-site mechanism at the pituitary and hypothalamus. Models with intact hypothalamic–pituitary connections and models with disconnection were given GHRH, GHRP-6, or both. In intact models, the highest GH levels occurred with the combination, followed by GHRP-6 alone, then GHRH alone. In disconnected models, the lowest GH levels were seen with the combination; GHRH alone resembled controls, and GH fell with GHRP-6 alone. The authors proposed two possibilities: GHRP-6 acts primarily in the presence of GHRH, and it may also act on the hypothalamic–pituitary axis to produce its effects.
Researchers have also discussed a potential affinity of GHRP-6 for CD36, a receptor implicated in lipid handling, phagocytosis, inflammation, and regulation of angiogenesis. Through these pathways, CD36-related signaling could contribute to observed effects in metabolic and tissue models.
Chemical Makeup
Molecular Formula: C₄₆H₅₆N₁₂O₆
Molecular Weight: 873.03 g/mol
Other Known Titles: Growth Hormone Releasing Peptide-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2; UNII-87616PU19N; CHEMBL410920; DTXSID80428423; CAS 87616-84-0
Research and Clinical Studies
GHRP-6 Peptide and Hypothyroidism
Because hypothyroidism is commonly linked with reduced GH secretion, one study evaluated whether GHRP-6 could mitigate this reduction. Models were randomized to various concentrations of GHRH and GHRP-6. GH levels rose more with GHRP-6 alone and with the GHRP-6 + GHRH combination than with GHRH alone. The authors suggested GHRP-6 may differ from GHRH in part by acting as a functional antagonist of somatostatin at the pituitary, which could explain the stronger response in hypothyroid settings.
GHRP-6 Peptide and Cortisol Hormone Release
In a night-time study of hormone release and sleep EEG, models received GHRP-6 or placebo. Following GHRP-6, secretion of both GH and ACTH/cortisol increased. During the first half of the night, cortisol output and stage-2 sleep were higher, while other EEG measures were largely unchanged. The results support GH-releasing activity and suggest engagement of the hypothalamic–pituitary axis affecting cortisol.
GHRP-6 Peptide and Organ Function
Work examining injury and multiple-organ failure assessed GHRP-6 alone and with epidermal growth factor (EGF). In epithelial models, GHRP-6 increased cell migration three-fold over control without boosting proliferation. In a separate injury model, GHRP-6 reduced hepatic and intestinal damage and lipid peroxidation by roughly 50–85%, with additional benefit when paired with EGF.
GHRP-6 Peptide and GI Transit
An alloxan-induced diabetes model was used to study delayed gastrointestinal transit. Diabetes reduced gastric emptying (GE), intestinal transit (IT), and colonic transit (CT). After GHRP-6 exposure at interval doses, GE and IT improved while CT remained unchanged.
GHRP-6 Peptide and Neuroprotection
GHRP-6 has been investigated for potential neuroprotective effects via the brain IGF-1 system. After a week of exposure, IGF-1 mRNA increased in the hypothalamus, cerebellum, and hippocampus (but not cortex). IGF-1 receptor and IGFBP-2 expression were unchanged, while phosphorylation of Akt and BAD rose in regions with higher IGF-1, consistent with activation of cell-survival pathways. Bcl-2 increased and Bax was unchanged, suggesting a shift toward anti-apoptotic signaling. IGFBP-5 also rose, especially in the hypothalamus.
GHRP-6 Peptide and Muscle Tissue
Some studies suggest anabolic potential, possibly through stimulation of GH and downstream IGF-1. In cultured myoblasts, GHRP-6 increased myogenic markers, IGF-1, collagen type I, and metabolic activity. In human pituitary testing, GHRP-6 elicited GH peaks and exposure (AUC) greater than those reported with GHRH. Another study reported a GH peak around 15.4 μg/L with GHRP-6 versus a physiological maximum near 5.5 μg/L.
GHRP-6 Peptide and Tissue Recovery
Beyond GH pathways, GHRP-6 is proposed to act via ghrelin and CD36 receptors in models of injury and inflammation. In mice, 30 days of exposure was associated with faster wound closure and reduced hypertrophic scarring, alongside lower inflammatory and fibrotic cytokines. In a combined radiation-and-burn model, ghrelin-receptor signaling reduced pro-inflammatory mediators such as TNF-α and favorably modulated healing pathways. In a liver-injury model, 60 days of GHRP-6 coincided with decreases in fibrosis, including reductions in TGF-β and CTGF, and marked declines in fibrotic area and nodularity.
GHRP-6 Peptide is available
for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.
References:
- Rico M, Lorenzo MT, Pazo JA, Vega FV, De la Cruz LF. GHRP-6 in heifer and cow adenohypophisial cells separated by elutriation. J Physiol Biochem. 1999 Mar;55(1):33-9. PMID: 10494658.
- Berlanga-Acosta, Jorge et al. “Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects.” Clinical Medicine Insights. Cardiology vol. 11 1179546817694558. 2 Mar. 2017, doi:10.1177/1179546817694558. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392015/
- Bowers, C.Y., et al (2012). Ghrelin: A history of its discovery. In Ghrelin in Health and Disaeas (pp. 1-35), Human press Inc. https://mayoclinic.pure.elsevier.com/en/publications/ghrelin-a-history-of-its-discovery
- Naushira Pandya, Roberta DeMott-Friberg, Cyril Y. Bowers, Ariel L. Barkan, Craig A. Jaffe, Growth Hormone (GH)-Releasing Peptide-6 Requires Endogenous Hypothalamic GH-Releasing Hormone for Maximal GH Stimulation, The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 4, 1 April 1998, Pages 1186–1189. https://academic.oup.com/jcem/article-abstract/83/4/1186/2865313
- Popovic V, Damjanovic S, Micic D, Djurovic M, Dieguez C, Casanueva FF. Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalamic level. J Clin Endocrinol Metab. 1995 Mar;80(3):942-7. doi: 10.1210/jcem.80.3.7883854. PMID: 7883854. https://pubmed.ncbi.nlm.nih.gov/7883854/
- Demers, A., McNicoll, N., Febbraio, M., Servant, M., Marleau, S., Silverstein, R., & Ong, H. (2004). Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study. The Biochemical journal, 382(Pt 2), 417–424. https://doi.org/10.1042/BJ20040036
- Pimentel-Filho FR, Ramos-Dias JC, Ninno FB, Façanha CF, Liberman B, Lengyel AM. Growth hormone responses to GH-releasing peptide (GHRP-6) in hypothyroidism. Clin Endocrinol (Oxf). 1997 Mar;46(3):295-300. doi: 10.1046/j.1365-2265.1997.1270942.x. https://pubmed.ncbi.nlm.nih.gov/9156038/
- Frieboes RM, Murck H, Maier P, Schier T, Holsboer F, Steiger A. Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man. Neuroendocrinology. 1995 May;61(5):584-9. https://doi.org/10.1159/000126883
- Cibrián D, Ajamieh H, Berlanga J, León OS, Alba JS, Kim MJ, Marchbank T, Boyle JJ, Freyre F, Garcia Del Barco D, Lopez-Saura P, Guillen G, Ghosh S, Goodlad RA, Playford RJ. Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failure. Clin Sci (Lond). 2006 May;110(5):563-73. https://pubmed.ncbi.nlm.nih.gov/16417467/
- Zheng, Q., Qiu, W. C., Yan, J., Wang, W. G., Yu, S., Wang, Z. G., & Ai, K. X. (2008). Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice. World journal of gastroenterology, 14(30), 4795–4799. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739343/
- Kristina Szabadfi, et al., Therapeutic Areas I: Central Nervous System, Pain, Metabolic Syndrome, Urology, Gastrointestinal and Cardiovascular, in Comprehensive Medicinal Chemistry II, 2007. https://www.sciencedirect.com/topics/medicine-and-dentistry/alloxan
- Frago LM, Pañeda C, Dickson SL, Hewson AK, Argente J, Chowen JA. Growth hormone (GH) and GH-releasing peptide-6 increase brain insulin-like growth factor-I expression and activate intracellular signaling pathways involved in neuroprotection. Endocrinology. 2002 Oct;143(10):4113-22. doi: 10.1210/en.2002-220261. PMID: 12239123.
- Lim, C. J., Jeon, J. E., Jeong, S. K., Yoon, S. J., Kwon, S. D., Lim, J., Park, K., Kim, D. Y., Ahn, J. K., & Kim, B. W. (2015). Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I. BMB reports, 48(9), 501–506. https://doi.org/10.5483/bmbrep.2015.48.9.258
- Cordido, F., Peñalva, A., Dieguez, C., & Casanueva, F. F. (1993). Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. The Journal of clinical endocrinology and metabolism, 76(4), 819–823. https://doi.org/10.1210/jcem.76.4.8473389
- Frieboes, R. M., Murck, H., Maier, P., Schier, T., Holsboer, F., & Steiger, A. (1995). Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH and cortisol release in normal man. Neuroendocrinology, 61(5), 584–589. https://doi.org/10.1159/000126883
- Mendoza Marí, Y., Fernández Mayola, M., Aguilera Barreto, A., García Ojalvo, A., Bermúdez Alvarez, Y., Mir Benítez, A. J., & Berlanga Acosta, J. (2016). Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds. Plastic surgery international, 2016, 4361702. https://doi.org/10.1155/2016/4361702
- Liu, C., Huang, J., Li, H., Yang, Z., Zeng, Y., Liu, J., Hao, Y., & Li, R. (2016). Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats. Scientific reports, 6, 27499. https://doi.org/10.1038/srep27499
- Berlanga-Acosta, J., Vázquez-Blomquist, D., Cibrián, D., Mendoza, Y., Ochagavía, M. E., Miranda, J., ... & Guillén-Nieto, G. E. (2012). Growth Hormone Releasing Peptide 6 (GHRP6) reduces liver fibrosis in CCl4 chronically intoxicated rats. Biotecnología Aplicada, 29(2), 60-72.
Dr. Marinov
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.