Growth hormone-releasing hexapeptide (GHRP-6)
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Product Description
Growth hormone-releasing hexapeptide (GHRP-6) is a synthetic six-amino-acid peptide that acts as a powerful and selective stimulus for pituitary growth hormone (GH) secretion. By binding to the ghrelin receptor (GHSR-1a) in the hypothalamus and pituitary, it bypasses the classical GHRH pathway, blocks the inhibitory hormone somatostatin, and rapidly elevates intracellular calcium to trigger GH release without disturbing other pituitary hormones. In cultured rat pituitary cells GHRP-6 evokes GH output comparable to GHRH, while in humans the combined GHRH+GHRP-6 test is highly reproducible and amplifies GH reserve assessment; conversely, the response is blunted in obesity and virtually abolished in Prader-Willi syndrome, indicating that its diagnostic power lies in revealing subtle hypothalamo-pituitary dysfunction. Although developed primarily as a research tool, these properties have made GHRP-6 a lead candidate for evaluating—and potentially treating—GH deficiency in children and adults.
Synthesis and Production
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Synthetic Origin: GHRP-6 is a synthetic, non-natural peptide. It was first developed in the early 1980s as part of a series of Growth Hormone-Releasing Peptides (GHRPs).
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Amino Acid Sequence: The peptide sequence is His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂.
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Key Structural Features: The presence of D-amino acids (D-Tryptophan and D-Phenylalanine) is a crucial aspect of its design, contributing to its metabolic stability and potency by making it resistant to enzymatic degradation. The C-terminal is modified to an amide (-NH₂), which is also important for its biological activity and stability.
Uses and Applications
GHRP-6 has been investigated for a wide range of biological effects, primarily driven by its ability to stimulate Growth Hormone (GH) secretion. Its applications are predominantly in the research and experimental therapeutic domains.
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Primary Endocrine Effect: Potent stimulation of GH secretion from the pituitary gland, both in vitro and in vivo. This effect is synergistic with the natural Growth Hormone-Releasing Hormone (GHRH).
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Cytoprotection and Cardioprotection (Major Research Focus):
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Cardioprotection: Extensive evidence shows GHRP-6 protects the heart from ischemia/reperfusion injury, reduces infarct size, improves left ventricular function in models of dilated cardiomyopathy, and exerts a positive inotropic effect. It has shown efficacy in animal models (rats, hamsters, pigs, dogs) and early human studies in patients with heart failure or undergoing bypass surgery.
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Multiorgan Cytoprotection: Demonstrates protective effects in other organs, including reducing damage in hepatic ischemia/reperfusion, attenuating lung, kidney, and intestinal injuries, and preventing gastric mucosal damage.
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Proposed Mechanisms: Activation of cell survival pathways (PI-3K/AKT1), reduction of reactive oxygen species (ROS), enhancement of antioxidant defenses, and anti-inflammatory actions.
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Anti-fibrotic Effects: Shown to reduce fibrosis in models of liver cirrhosis and hypertrophic scars, potentially by downregulating profibrotic cytokines like TGF-β1.
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Anti-inflammatory Effects: Attenuates the inflammatory response in models of endotoxemia and arthritis by reducing pro-inflammatory cytokines (TNF-α, IL-6).
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Myotropic/Anabolic Effects: Promotes muscle anabolism and prevents atrophy, suggesting potential use against sarcopenia and cardiac cachexia.
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Neuroprotection: In combination with Epidermal Growth Factor (EGF), it has shown benefits in experimental models of multiple sclerosis, peripheral axonopathy, and brain ischemia.
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Stimulation of Appetite: A known effect, with potential application for cancer-associated anorexia-cachexia syndrome.
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Diagnostic Tool: The combination of GHRP-6 with GHRH has been evaluated as a highly reproducible and potent test for diagnosing growth hormone reserve/deficiency in adults.
Chemical and Physical Properties
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Molecular Formula: C₄₆H₅₆N₁₂O₆
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Molecular Weight: 873.0 g/mol
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Monoisotopic Mass: 872.44457755 Da
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Other Computed Physicochemical Properties:
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XLogP3: 1.9 (indicates moderate lipophilicity)
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Hydrogen Bond Donor Count: 11
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Hydrogen Bond Acceptor Count: 9
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Rotatable Bond Count: 23
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Topological Polar Surface Area (TPSA): 301 Ų
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Heavy Atom Count: 64
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Defined Atom Stereocenter Count: 6
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Mechanism of Action: Binds to and activates two key receptors:
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GHS-R1a (Ghrelin Receptor): The primary target, leading to GH release.
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CD36 (Scavenger Receptor): Also mediates some of its cardioprotective and metabolic effects.
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Stability and Administration: Noted to be effective when administered intravenously and orally. Its synthetic structure with D-amino acids contributes to its stability.
Safety and Handling
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Preclinical Safety Profile: GHRP-6 exhibits a "broad safety profile in preclinical and clinical settings."
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Human Clinical Trial: A specific clinical trial in healthy human volunteers is cited, which demonstrated that intravenous GHRP-6 was safe in a dose scale-up study.
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Drug Interaction Study: No pharmacological interaction was found between GHRP-6 and the cardiovascular drug metoprolol, suggesting a favorable profile for co-administration.
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Side Effects (from research contexts): The primary noted side effect is transient hyperglycemia, which is common to GH secretagogues. Its potent stimulation of GH can also lead to effects associated with elevated GH/IGF-1 levels.
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Handling: As a peptide, it is typically handled as a lyophilized powder that requires reconstitution and proper storage for research use.