Growth Hormone-Releasing Peptide-6 (GHRP-6) is a synthetic hexapeptide consisting of the amino acid sequence His-DTrp-Ala-Trp-DPhe-Lys-NH2. It is a member of a class of peptides known as Growth Hormone Secretagogues (GHSs) and functions primarily to stimulate the release of growth hormone (GH) from the anterior pituitary gland (McDowell et al., 1995; (Diéguez & Casanueva, 2000; . GHRP-6 exhibits its effects by interacting with specific receptors in the hypothalamus and the pituitary gland, thereby promoting GH secretion in a dose-dependent manner (Argente et al., 1996; Badger et al., 1984).
The design of GHRP-6 is rooted in prior research that explored various peptide analogs for their ability to stimulate GH release. Studies have demonstrated that GHRP-6 is more potent than its predecessors due to modifications that enhance its stability and bioactivity, including the receptor-binding characteristics shared among peptides like ghrelin (McDowell et al., 1995; (Diéguez & Casanueva, 2000; . GHRP-6 not only promotes GH release but is also known to influence other hormonal pathways, enhancing the secretion of adrenocorticotropic hormone (ACTH) and cortisol (Sá et al., 2010). This multi-faceted action showcases its potential efficacy in various physiological and pathological states (Locatelli et al., 1994).
Research indicates that GHRP-6 possesses the capacity to augment physiological functions beyond stimulating growth hormone. Studies have documented its roles in improving animal growth performance, as observed in aquaculture settings where GHRP-6 immersion treatments significantly enhance shrimp growth (Martı́nez et al., 2017; Álvarez-Torres et al., 2025). Furthermore, GHRP-6 has been reported to foster healing processes in tissue repair scenarios by down-regulating inflammatory cytokines, demonstrating its utility in improving wound healing and mitigating inflammation (Mendoza‐Marí et al., 2016; Cibrián et al., 2006).
Additionally, the mechanism of action of GHRP-6 involves modulating neuroendocrine responses via hypothalamic pathways, where it interacts with growth hormone-releasing hormone (GHRH) and somatostatin to influence GH secretion dynamics (Diéguez & Casanueva, 2000; Badger et al., 1984). The distinct structure-activity relationships of GHRP-6 reveal that despite its relatively simple hexapeptide structure, it elicits complex biological effects that underscore its significance in both research and potential therapeutic applications (Ferro et al., 2016).
In summary, GHRP-6 is a vital peptide in the study of growth hormone regulation, characterized by its ability to significantly promote GH release and engage in various biological processes, making it an important subject for further research in endocrinology and related fields.
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References:
Argente, J., García‐Segura, L., Pozo, J., & Chowen, J. (1996). Growth hormone-releasing peptides: clinical and basic aspects. Hormone Research, 46(4-5), 155-159. https://doi.org/10.1159/000185015
Badger, T., Millard, W., McCormick, G., Bowers, C., & Martin, J. (1984). The effects of growth hormone (gh)-releasing peptides on gh secretion in perifused pituitary cells of adult male rats*. Endocrinology, 115(4), 1432-1438. https://doi.org/10.1210/endo-115-4-1432
Cibrián, D., Ajamieh, H., Berlanga, J., León, O., Alba, J., Kim, M., … & Playford, R. (2006). Use of growth-hormone-releasing peptide-6 (ghrp-6) for the prevention of multiple organ failure. Clinical Science, 110(5), 563-573. https://doi.org/10.1042/cs20050374
Diéguez, C. and Casanueva, F. (2000). Ghrelin: a step forward in the understanding of somatotroph cell function and growth regulation. Acta Endocrinologica, 413-417. https://doi.org/10.1530/eje.0.1420413
Ferro, P., Krotov, G., Zvereva, I., Родченков, Г., & Segura, J. (2016). Structure‐activity relationship for peptídic growth hormone secretagogues. Drug Testing and Analysis, 9(1), 87-95. https://doi.org/10.1002/dta.1947
Locatelli, V., Grilli, R., Torsello, A., Cella, S., Wehrenberg, W., & Müller, E. (1994). Growth hormone-releasing hexapeptide is a potent stimulator of growth hormone gene expression and release in the growth hormone—releasing hormone—deprived infant rat. Pediatric Research, 36(2), 169-174. https://doi.org/10.1203/00006450-199408000-00006
Martı́nez, R., Carpio, Y., Arenal, A., Lugo, J., Morales, R., Martín, L., … & Estrada, M. (2017). Significant improvement of shrimp growth performance by growth hormone-releasing peptide-6 immersion treatments. Aquaculture Research, 48(9), 4632-4645. https://doi.org/10.1111/are.13286
McDowell, R., Elias, K., Stanley, M., Burdick, D., Burnier, J., Chan, K., … & Jacobsen, N. (1995). Growth hormone secretagogues: characterization, efficacy, and minimal bioactive conformation.. Proceedings of the National Academy of Sciences, 92(24), 11165-11169. https://doi.org/10.1073/pnas.92.24.11165
Mendoza‐Marí, Y., Fernández‐Mayola, M., Barreto, A., García‐Ojalvo, A., Alvarez, Y., Benítez, A., … & Acosta, J. (2016). Growth hormone-releasing peptide 6 enhances the healing process and improves the esthetic outcome of the wounds. Plastic Surgery International, 2016, 1-11. https://doi.org/10.1155/2016/4361702
Sá, L., Nascif, S., Correa‐Silva, S., Molica, P., Vieira, J., Dib, S., … & Lengyel, A. (2010). Effects of ghrelin, growth hormone–releasing peptide–6, and growth hormone–releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus. Metabolism, 59(10), 1536-1542. https://doi.org/10.1016/j.metabol.2010.01.021
Álvarez-Torres, D., Martı́nez, R., Moreno, P., Alonso, M., García‐Rosado, E., Estrada, M., … & Béjar, J. (2025). Anti-nervous necrosis virus activity of the growth hormone releasing peptide-6, ghrp-6. Aquaculture International, 33(4). https://doi.org/10.1007/s10499-025-01987-w
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