GHRP-6 is a synthetic, first-generation hexapeptide growth hormone secretagogue (GHS). It was developed in the 1980s through systematic modification of the met-enkephalin structure to create a compound with potent, dose-dependent growth hormone (GH) releasing activity, independent of the endogenous hypothalamic hormone growth hormone-releasing hormone (GHRH). Its discovery was pivotal in identifying and characterizing the ghrelin/GHS receptor pathway, a major physiological regulator of GH secretion and appetite. GHRP-6 has served as a fundamental research tool for understanding GH regulation and the therapeutic potential of GH secretagogues in conditions like growth hormone deficiency, cachexia, and tissue repair. Its significance lies in being a prototype that led to the discovery of the endogenous ligand ghrelin and the broader GHS receptor family.
Quick Facts
| Also Known As | GHRP-6, Hexarelin (note: Hexarelin is a distinct but closely related analog), GH-releasing peptide-6 |
|---|---|
| Sequence | His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 |
| Molecular Formula | C46H56N12O6 |
| Molecular Weight | 873.0 Da |
| PubChem CID | 4345065 |
Research Parameters
| Half-Life | Approximately 15-30 minutes in rodent models; human pharmacokinetics are not fully established. |
|---|---|
| Stability | Lyophilized powder is stable for at least 24 months when stored at -20°C, protected from light and moisture. After reconstitution in bacteriostatic water, the solution is typically stable for 14-28 days when refrigerated at 2-8°C, though specific data varies. |
| Solubility | Bacteriostatic Water (0.9% benzyl alcohol) or Sterile Water for injection. |
| Vial Size | 5 mg |
| Storage (Lyophilized) | -20°C, protected from light and moisture. |
| Storage (Reconstituted) | 2-8°C (refrigerated), protected from light. Use within the stability period recommended by the manufacturer/research supplier. |
| Typical Research Dose | In rodent research: 10-300 mcg/kg per injection. |
| Cycle Parameters | Research protocols vary widely. A common chronic study design involves daily subcutaneous injections for 1 to 4 weeks continuously to assess effects on the GH/IGF-1 axis and body composition. |
| Amino Acid Count | 9 |
Mechanism of Action
GHRP-6 exerts its primary effects by acting as a potent agonist at the growth hormone secretagogue receptor (GHS-R), specifically the GHS-R1a subtype. This receptor is distinct from the receptor for growth hormone-releasing hormone (GHRH). Activation triggers intracellular signaling cascades that culminate in pulsatile release of growth hormone from the anterior pituitary somatotroph cells.
GHS-R1a Activation: GHRP-6 binds to and activates the GHS-R1a, a G-protein coupled receptor. This binding is highly specific and does not involve GHRH.
Intracellular Signaling: Receptor activation primarily stimulates the phospholipase C (PLC) pathway, leading to inositol trisphosphate (IP3) production and mobilization of intracellular calcium. It also modulates other pathways, including protein kinase C (PKC) and mitogen-activated protein kinase (MAPK).
Synergy with GHRH: GHRP-6 acts synergistically with endogenous GHRH. The combined action on distinct receptors and signaling pathways produces a greater GH release than either stimulus alone, suggesting complementary mechanisms at the pituitary level.
Secondary Neuroendocrine Effects: Beyond direct pituitary action, GHRP-6 may also influence hypothalamic neurons, potentially inhibiting somatostatin (GH release-inhibiting hormone) tone, which further facilitates GH secretion.
Research Applications
Growth Hormone Research: GHRP-6 is a standard tool for stimulating GH secretion in animal and ex vivo models. It is used to study the physiology of the GH/IGF-1 axis, pulsatile hormone release, and the pharmacology of GHS-R agonists.
Cachexia and Muscle Wasting: Research in animal models of cancer, renal failure, and aging has investigated GHRP-6 for its potential to counteract muscle catabolism. Its GH-releasing and possible direct anabolic effects may help preserve lean body mass and improve nutritional status.
Cardioprotection and Tissue Healing: Preclinical studies suggest GHRP-6 may have cytoprotective and anti-inflammatory properties independent of GH. Research areas include reducing ischemic damage in cardiac tissue, promoting healing of gastric ulcers, and enhancing recovery from musculoskeletal injuries.
Metabolic Regulation: Studies explore its effects on appetite stimulation (via GHS-R in the hypothalamus), lipid metabolism, and glucose homeostasis, linking the ghrelin system to energy balance.
Safety & Side Effects
In animal studies, GHRP-6 is generally well-tolerated at research doses. Reported effects are primarily extensions of its pharmacological action: transient increases in blood glucose and prolactin, and appetite stimulation. Anecdotal reports from research contexts sometimes mention mild, transient flushing or hunger pangs immediately after administration. Theoretical concerns based on its mechanism include the potential for acromegaly-like symptoms with extreme long-term, high-dose exposure due to sustained elevation of GH and IGF-1. Its safety profile in humans is not fully established.
Dosage Information
This information is derived from preclinical research studies only and does not constitute clinical guidance.
In rodent research, typical subcutaneous or intraperitoneal doses range from 10 to 300 mcg/kg, administered once or twice daily. Dosing frequency and duration vary by study design, from acute single injections to chronic administration over several weeks. Common research protocols involve daily injections for 1-4 weeks to assess chronic effects on GH/IGF-1 axis, body composition, or specific disease models.
References
Bowers, C.Y., Momany, F.A., Reynolds, G.A., Hong, A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology, 1984.
Smith, R.G., Cheng, K., Schoen, W.R., Pong, S.S., Hickey, G., Jacks, T., Butler, B., Chan, W.W., Chaung, L.Y., Judith, F. A nonpeptidyl growth hormone secretagogue. Science, 1993.
Korbonits, M., Grossman, A.B. Ghrelin: update on a novel hormonal system. European Journal of Endocrinology, 2004.
Torsello, A., Luoni, M., Schweiger, F., Grilli, R., Guidi, M., Bresciani, E., Deghenghi, R., Muller, E.E., Locatelli, V. Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release. European Journal of Pharmacology, 1998.
Hataya, Y., Akamizu, T., Takaya, K., Kanamoto, N., Ariyasu, H., Saijo, M., Moriyama, K., Shimatsu, A., Kojima, M., Kangawa, K., Nakao, K. A low dose of ghrelin stimulates growth hormone (GH) release synergistically with GH-releasing hormone in humans. Journal of Clinical Endocrinology & Metabolism, 2001.
Camanni, F., Ghigo, E., Arvat, E. Growth hormone-releasing peptides and their analogs. Frontiers in Neuroendocrinology, 1998.