GHRP-2 is a synthetic, potent, and selective hexapeptide growth hormone secretagogue (GHS). It was developed in the late 1980s and early 1990s as part of a series of peptides designed to mimic the activity of the endogenous hormone ghrelin by stimulating the ghrelin/growth hormone secretagogue receptor (GHSR). Its discovery was pivotal in elucidating the ghrelin system and provided a powerful research tool for studying growth hormone (GH) release independent of the hypothalamic growth hormone-releasing hormone (GHRH) pathway.
The significance of GHRP-2 lies in its ability to potently and synergistically stimulate pulsatile GH secretion, leading to increased insulin-like growth factor 1 (IGF-1) levels. It has been extensively used in preclinical and clinical research to investigate the roles of GH and IGF-1 in growth, metabolism, body composition, and tissue repair. Unlike GHRH, its action is not inhibited by somatostatin, making it a robust stimulator even in states of high somatostatin tone.
Quick Facts
| Also Known As | GHRP-2, KP-102, D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2 |
|---|---|
| Sequence | D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH2 |
| Molecular Formula | C45H55N9O6 |
| Molecular Weight | 818.0 Da |
| PubChem CID | 6918245 |
Research Parameters
| Half-Life | Approximately 15-30 minutes in humans (plasma half-life). The biological effect on GH secretion lasts for several hours. |
|---|---|
| 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, although researchers should consult specific stability studies. |
| Solubility | Bacteriostatic Water (0.9% benzyl alcohol) or Sterile Water for Injection. |
| Vial Size | 5 mg |
| Storage (Lyophilized) | -20°C or below, protected from light and moisture. |
| Storage (Reconstituted) | 2-8°C (refrigerated), protected from light. Use within the stability period indicated for the chosen solvent (e.g., 28 days for bacteriostatic water). |
| Typical Research Dose | 100-300 mcg per dose (for a ~70-100 kg individual) or 1-3 mcg/kg. |
| Cycle Parameters | In research studies, common protocols involve once or twice daily subcutaneous administration for periods of 4 to 12 weeks. Some protocols may include cyclical administration (e.g., 5 days on, 2 days off) to mimic natural pulsatility, but continuous daily dosing is also studied. |
| Amino Acid Count | 11 |
Mechanism of Action
GHRP-2 acts primarily as a potent agonist at the growth hormone secretagogue receptor (GHSR-1a), which is the endogenous receptor for ghrelin. Its mechanism involves direct pituitary action and hypothalamic modulation to stimulate growth hormone (GH) release.
GHSR-1a Agonism: GHRP-2 binds to and activates the GHSR-1a on somatotroph cells in the anterior pituitary. This activation triggers the Gq/11 protein signaling pathway, leading to phospholipase C activation, inositol trisphosphate (IP3) formation, and intracellular calcium mobilization, which directly stimulates GH secretion.
Hypothalamic Integration: GHRP-2 also acts on GHSR-1a receptors in the hypothalamus. It stimulates the release of endogenous GHRH and concurrently inhibits somatostatin secretion. This dual hypothalamic action amplifies the pituitary GH release.
Synergy with GHRH: GHRP-2 exhibits a strong synergistic effect when co-administered with GHRH. The combined action results in a significantly greater GH release than the sum of their individual effects, a key feature exploited in diagnostic and research settings.
Ghrelin Mimicry: As a ghrelin mimetic, GHRP-2 shares downstream effects, including potential modulation of appetite and metabolic pathways via central nervous system GHSR-1a receptors, although its primary research focus is on GH axis stimulation.
Research Applications
Growth Hormone Deficiency Research: GHRP-2 is a valuable tool for investigating the pathophysiology and potential treatments for growth hormone deficiency (GHD). Studies have explored its diagnostic utility in provocative testing for GHD and its therapeutic potential to restore physiological GH pulsatility and improve body composition.
Metabolic and Body Composition Studies: Research has investigated the effects of GHRP-2 on lipid metabolism, lean body mass, and fat mass. Its ability to increase IGF-1 levels makes it a model compound for studying anabolic and metabolic effects in models of catabolism, aging, or obesity.
Tissue Repair and Regeneration: Due to the anabolic and proliferative effects of GH and IGF-1, GHRP-2 has been studied in contexts of wound healing, muscle repair, and bone formation. Research explores its potential to accelerate recovery from injury, surgery, or burns by promoting protein synthesis and cellular regeneration.
Cardiovascular Research: Some studies have examined the cardioprotective and inotropic effects of GHRP-2, independent of GH release, potentially mediated through direct GHSR-1a activation in cardiac tissue. This includes research on heart failure and ischemic injury models.
Safety & Side Effects
From controlled human and animal studies, GHRP-2 is generally well-tolerated at research doses. The most commonly reported acute side effects are related to its ghrelin-mimetic activity and include transient hunger, flushing, and mild dizziness shortly after injection. Mild, transient increases in cortisol and prolactin have been observed.
Theoretical concerns from chronic use, based on the known effects of elevated GH/IGF-1, include potential for insulin resistance, fluid retention (edema), arthralgia, and acral growth (enlargement of hands and feet). There is a theoretical risk of promoting the growth of pre-existing malignancies due to the mitogenic properties of IGF-1. Anecdotal reports from non-clinical use sometimes mention headaches and lethargy. Comprehensive long-term safety data in humans is limited.
Dosage Information
This information is derived from published research studies only and is not a recommendation for human use.
In clinical research studies, GHRP-2 is typically administered via subcutaneous injection. Common research doses range from 1 to 3 mcg/kg per administration. In adult human studies, fixed doses of 100 mcg or 200 mcg are frequently used. Administration frequency in research protocols is often once or twice daily. The duration of administration in studies varies from single-dose diagnostic tests to chronic administration over several weeks (e.g., 2-8 weeks) to assess metabolic and body composition effects.
References
Bowers, C.Y., et al. 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, 114(5), 1537-1545.
Ghigo, E., et al. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man. Journal of Clinical Endocrinology & Metabolism, 1994, 78(3), 693-698.
Arvat, E., et al. Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH. Peptides, 1995, 16(6), 1091-1097.
Smith, R.G., et al. Peptidomimetic regulation of growth hormone secretion. Endocrine Reviews, 1997, 18(5), 621-645.
Hataya, Y., et al. A low dose of GHRP-2 stimulates GH release in patients with severe adult GH deficiency. Clinical Endocrinology, 2003, 58(4), 448-455.
Broglio, F., et al. Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone. Journal of Clinical Endocrinology & Metabolism, 2001, 86(3), 1169-1174.