Synthetic peptides called GH-releasing peptides (GHRPs) have effects on the pituitary somatotrophs, similar to GHRH, to promote the release of growth hormone (GH). Of these synthetic hormones, GHRP-6 has been the most studied in detail and is believed to act at both pituitary and hypothalamic sites. It is also known as the Growth Hormone Releasing Hexapeptide and it was developed to help increase the body’s natural production of growth hormone.
GHRP-6 acts as an agonist of the growth hormone secretagogue receptor. It instead stimulates the pituitary gland to secrete growth hormone into the bloodstream. The unique aspect of GHRP-6 is that it doesn’t interfere with the body’s natural hormonal balance. It simply encourages the system to continue what it naturally produces but in larger quantities.
The synthetic peptide GHRP-6 can stimulate growth hormone release similarly to the endogenous hormone ghrelin. However, GHRP-6’s structural differences from ghrelin suggested its mechanism of action may also differ. Recent structural analyses of the ghrelin receptor (GHSR1a) have uncovered how GHRP-6 activates this receptor to promote hormone secretion.
Although GHRP-6 does not contain the acyl modification essential for ghrelin binding to GHSR1a, it binds to an alternate site on the receptor. This induces a distinct conformational change compared to ghrelin, but still activates the same downstream signaling cascades. So while the binding interactions differ between the two ligands, GHRP-6 mimics the functional effects of ghrelin-stimulation of appetite and growth hormone release.
Structural characterization of GHRP-6 binding to GHSR1a establishes that synthetic growth hormone secretagogues can modulate this receptor through unique mechanisms. Identifying an alternative binding pocket and activation mode opens avenues for designing improved GHRP analogs.
The hormone ghrelin plays a pivotal role in the regulation of appetite and growth hormone secretion. It also has an effect on glucose and lipid metabolism. Recent research delved into inhibiting its actions in a porcine model by utilizing a receptor antagonist.
Pigs treated with the ghrelin blocker exhibited increased hepatic fatty acid oxidation and gluconeogenesis. The antagonist enhanced expression of genes involved in fat metabolism and glucose production in the liver. Serum growth hormone levels were also elevated, likely due to blocking the hormone’s negative feedback on its own release.
Researchers explored a therapeutic strategy to reverse hypogonadism and testicular dysfunction caused by anabolic steroid abuse. Male rabbits were treated with the anabolic agent oxymetholone to purposely induce hypogonadism. After one month, the rabbits predictably developed shrunken testes, depleted testosterone levels, and reduced sperm counts and motility.
To treat this iatrogenic hormonal dysfunction, the rabbits received a regimen of GHRP-6 and clomiphene citrate. GHRP-6 activates the body’s natural growth hormone output, known to stimulate testosterone production. Clomiphene directly stimulates gonadotropin secretion in the brain and testes to boost testosterone synthesis. This two-pronged approach successfully restored testicular size and function, returning testosterone to normal levels and rescuing fertility parameters.
CAS Number: 145177-42-0
Formula: C46H56N12O6
Sequence: His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Molar Mass: 873.032 g/mol
Half life: 2.5 hours
Class: Hexapeptide
Storage: Keep refrigerated upon reconstitution.
This preparation is for in vitro laboratory research purposes only by licensed professionals and is not approved by the FDA for bodily introduction of any kind into humans or animals. GHRP 6 is not a drug, food, supplement, or cosmetic and may not be misbranded, misused, or mislabeled as a drug, food, supplement, or cosmetic.
GHRP-6 (growth hormone releasing peptides 6) is a peptide that mimics Ghrelin to stimulate hunger and increase plasma Growth hormone.
The pulsatile release of natural GH by GHRP-6 is received more naturally by mammalian bodies than the continuous growth hormone releasing hormone from exogenous GH administration. Secretagogues such as GHRP6 or Ipamorelin may also prevent the shutdown of natural pituitary GH release often observed with exogenous GH administration.
A substantial increase in appetite and fluid retention has been observed in test subjects administered GHRP-6 and this may increase cortisol or induce connective tissue discomfort.
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1. Dawood, A. A., Al-Samarrai, R. R. H., & Husain, W. N. (2022, July). Growth hormone secretagogue GHRP-6 and clomiphene citrate (CC) for the treatment of hypogonadism induced by the anabolic steroid oxymetholone in male white rabbits. In AIP Conference Proceedings (Vol. 2450, No. 1). AIP Publishing.
2. Lei T, Buchfelder M, Fahlbusch R, Adams EF. Growth hormone releasing peptide (GHRP-6) stimulates phosphatidylinositol (PI) turnover in human pituitary somatotroph cells. J Mol Endocrinol. 1995 Feb;14(1):135-8. doi: 10.1677/jme.0.0140135. PMID: 7772238.
3. Wang, Y., Guo, S., Zhuang, Y., Yun, Y., Xu, P., He, X., … & Jiang, Y. (2021). Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. Nature Communications, 12(1), 5064.
4. Zhang, H., Yan, X., Lin, A., Xia, P., & Su, Y. (2023). Inhibition of ghrelin activity by the receptor antagonist [D-Lys3]-GHRP-6 enhances hepatic fatty acid oxidation and gluconeogenesis in a growing pig model. Peptides, 171041.
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