GHRP-6

-GHRP-6’s multifaceted role in GH modulation, energy homeostasis, and tissue protection continues to be a prominent focus in endocrine and metabolic research.

- Gastrointestinal Transit:In alloxan-induced diabetic mice, impaired gastric emptying and intestinal transit were significantly improved by GHRP-6 administration, while colonic transit remained unchanged.

- Neuroprotection:A one-week exposure to GHRP-6 in mouse models elevated IGF-1 mRNA levels in the hypothalamus, cerebellum, and hippocampus (not in the cortex). This was accompanied by increased phosphorylation of Akt and BAD, upregulation of the antiapoptotic protein Bcl-2, and enhanced IGFBP-5 expression in the hypothalamus, suggesting activation of IGF-1-mediated neuroprotective pathways.

- Muscle Anabolism:In cultured myoblasts, GHRP-6 enhanced expression of myogenic markers, IGF-1, and collagen type I, indicating anabolic effects. Comparative studies showed that GHRP-6 achieved GH peaks of approximately 15.7 ± 4.4 μg/L (AUC 674 ± 187 μg/L/90 min), exceeding those induced by GHRH (peak ~6.8 ± 1.1 μg/L, AUC 412 ± 71 μg/L/90 min).- Tissue Recovery:In murine models, chronic (30-day) GHRP-6 treatment accelerated wound healing and reduced hypertrophic scarring by attenuating inflammatory cytokines and fibrotic signals. In rat models of combined radiation and burn injury, GHRP-6 reduced TNF-α levels and, over 60 days, decreased liver fibrosis markers TGF-β and CTGF by 75% and over 60%, respectively.

-Hypothyroidism: In hypothyroid models, GHRP-6 (alone or with GHRH) elicits significantly higher GH secretion—possibly through somatostatin antagonism—compared to GHRH alone.
- Cortisol Release & Sleep: Administration of GHRP-6 enhances nocturnal GH and cortisol release, particularly increasing stage 2 sleep, without altering other EEG parameters.
- Organ Protection: GHRP-6 promotes a threefold increase in gut epithelial cell migration without affecting proliferation, and, in combination with EGF, reduces hepatic and intestinal damage and lipid peroxidation by 50–85% in experimental models.

ibrián 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

Molecular Formula: C₄₆H₅₆N₁₂O₆
- Molecular Weight: 873.03 g/mol
- Alternate Name: Growth Hormone Releasing Peptide-6