Product description
What is GHRP-2?
GHRP-2 (Growth Hormone-Releasing Peptide-2) is a synthetic hexapeptide with the sequence D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂, belonging to the class of growth hormone secretagogues (GHS). The compound was developed as part of a research program aimed at identifying molecules capable of stimulating the release of growth hormone (GH) from the pituitary gland through a mechanism independent of growth hormone-releasing hormone (GHRH).
Structurally, GHRP-2 is characterized by the presence of D-amino acids (D-Ala, D-2-Nal, D-Phe), which confer resistance to enzymatic degradation and extend the half-life compared with peptides composed exclusively of L-amino acids. Its molecular weight is approximately 818 Da, and its molecular formula is C₄₅H₅₅N₉O₆. The presence of non-natural amino acids such as D-2-naphthylalanine (D-2-Nal) is key to its high affinity for the growth hormone secretagogue receptor.
GHRP-2 acts as an agonist of the GHS-R1a receptor (Growth Hormone Secretagogue Receptor type 1a), which is also the natural receptor for ghrelin - an endogenous peptide hormone produced mainly in the stomach. Binding of GHRP-2 to GHS-R1a on pituitary somatotropes leads to cell depolarization, calcium influx, and pulsatile growth hormone release that mimics the physiological secretion pattern.
Compared with other peptides in this class, GHRP-2 is considered one of the most potent stimulators of GH secretion, outperforming GHRP-6 in this respect and being comparable to Ipamorelin in terms of specificity, although it shows somewhat stronger effects on appetite and prolactin.
Mechanism of action
GHS-R1a receptor activation - GHRP-2 binds to the growth hormone secretagogue receptor type 1a (GHS-R1a) on pituitary somatotropes. Activation of this G-protein-coupled receptor triggers a signaling cascade involving phospholipase C activation, phosphatidylinositol hydrolysis, mobilization of intracellular calcium, and activation of protein kinase C (PKC). In contrast to GHRH, this mechanism is independent of cyclic AMP (cAMP).
Synergy with endogenous GHRH - GHRP-2 requires the presence of endogenous GHRH to achieve a maximal GH response. Studies have shown that administration of a GHRH antagonist reduces the GH response to GHRP-2 by about 80-95%. The two pathways - GHRH and GHRP - act synergistically, with GHRH increasing GH synthesis and GHRP enhancing its release.
Somatostatin inhibition - GHRP-2 also acts at the hypothalamic level by inhibiting the release of somatostatin (SRIF), the main inhibitor of GH secretion. This dual mechanism - direct pituitary stimulation plus reduced inhibition by somatostatin - contributes to the strong GH-releasing effect.
Appetite stimulation - By activating GHS-R1a in the hypothalamus, GHRP-2 stimulates NPY (neuropeptide Y) neurons in the arcuate nucleus, leading to increased appetite. In humans, administration of GHRP-2 increases food intake by an average of 35.9% compared with placebo.
CD36 receptor binding - In addition to GHS-R1a, GHRP-2 and related peptides show affinity for the scavenger receptor CD36 (FAT/CD36), which may contribute to the observed cytoprotective and anti-inflammatory effects independent of GH release.
Scientific research directions
Research on GHRP-2 covers its effects on growth hormone secretion, cardioprotective functions, metabolism, and potential clinical applications.
Stimulation of growth hormone secretion
In studies on healthy volunteers, GHRP-2 consistently showed strong stimulation of GH release. A single intravenous dose (1 μg/kg) caused a multiple-fold increase in plasma GH concentration within minutes. The combination of GHRP-2 with GHRH produced a synergistic response, greatly exceeding the sum of the effects of the individual peptides. The GHRP-2 + GHRH test is used diagnostically to assess pituitary reserve in patients with suspected GH deficiency.
Cardioprotection and cardiovascular functions
Studies in animal models have shown that GHRP-2 has cardioprotective properties partly independent of GH release. In a rat model of doxorubicin-induced cardiomyopathy, GHRP-2 reduced myocardial damage and improved contractile function. The mechanism involves activation of the PI3K/AKT pathway, reduced oxidative stress, and inhibition of cardiomyocyte apoptosis.
Anti-inflammatory and myoprotective effects
In studies on arthritis models, GHRP-2 showed anti-inflammatory and cartilage-protective effects. The peptide reduced levels of pro-inflammatory mediators and inhibited extracellular matrix degradation. These effects are partly mediated by the CD36 receptor and are independent of elevated GH or IGF-1 levels.
Cachexia and sarcopenia
Because of its strong anabolic effect and appetite stimulation, GHRP-2 is being studied as a potential intervention in cachectic states associated with cancer, chronic obstructive pulmonary disease (COPD), and heart failure. The 35.9% increase in food intake observed in humans suggests therapeutic potential in these indications.
Growth hormone deficiency diagnostics
The GHRP-2 stimulation test is used in diagnosing growth hormone deficiency in children and adults. In combination with GHRH, this test shows high sensitivity and specificity in differentiating patients with true GH deficiency from healthy individuals.
Scientific context
GHRP-2 belongs to the family of growth hormone-releasing peptides (GHRPs), which also includes:
- GHRP-6 - the first widely studied GHRP, with a stronger effect on appetite
- GHRP-1 - less potent, used less often
- Hexarelin - potent, but with a greater effect on cortisol and prolactin
- Ipamorelin - newer, most selective, with minimal effects on other hormones
Compared with the compounds above, GHRP-2 offers a balance between potency and selectivity. It is a stronger GH stimulator than GHRP-6, but causes a smaller increase in cortisol than Hexarelin. Its effects on prolactin and appetite are moderate - stronger than Ipamorelin, but weaker than GHRP-6.
The history of GHRP-2 dates back to the 1980s, when Cyril Bowers' team discovered that certain met-enkephalin analogues could release growth hormone. Subsequent structural optimization led to the creation of GHRP-2 as one of the most potent members of this class.
GHRP-2 is on the WADA (World Anti-Doping Agency) list of prohibited substances as an anabolic substance, reflecting its potential for misuse in sport.
Safety profile in studies
General tolerance - In clinical studies, GHRP-2 has shown a good safety profile during short-term use. The peptide was well tolerated at doses used in diagnostic and research protocols.
Adverse effects - Observed symptoms include increased appetite and hunger (a pharmacological effect), transient facial flushing and warmth, fluid retention and edema with longer use, a temporary increase in prolactin and cortisol, and injection-site reactions.
Effects on other hormones - Unlike some other GHRPs, GHRP-2 causes a moderate increase in prolactin and cortisol. These effects are temporary and subside after discontinuation of the peptide. With long-term use, partial receptor desensitization may occur, reducing the GH response.
Interactions - GHRP-2 shows synergy with GHRH and antagonism with somatostatin. Potential interactions with drugs affecting the GH axis require caution.
Regulatory status - GHRP-2 is not approved by the FDA for clinical use in the United States. It is used in some countries for diagnostic purposes (GH stimulation testing). It is on the WADA prohibited list. It is available as a research peptide.
Bibliography – latest scientific studies
- Berlanga-Acosta J et al. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects. Clin Med Insights Cardiol. 2017;11:1179546817694558. PMC
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- Smith RG. Development of growth hormone secretagogues. Endocr Rev. 2005;26(3):346-360. PubMed
- Popovic V et al. Serum ghrelin levels in patients with growth hormone deficiency evaluated with growth hormone releasing hormone-growth hormone releasing peptide-2 test. J Clin Endocrinol Metab. 2004;89(11):5478-5483. PubMed
- Nass R et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med. 2008;149(9):601-611. PMC
- Muccioli G et al. Growth hormone-releasing peptides and the cardiovascular system. Ann Endocrinol (Paris). 2000;61(1):27-31. PubMed
- Vestergaard PF et al. Ghrelin and growth hormone secretagogues in health and disease. Pituitary. 2020;23(5):500-520. PubMed
- Cordido F et al. Effect of combined administration of growth hormone (GH)-releasing hormone, GH-releasing peptide-6, and pyridostigmine in normal and obese subjects. Metabolism. 1995;44(6):745-748. PubMed
- Laferrère B et al. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. J Clin Endocrinol Metab. 2005;90(2):611-614. PubMed
- Micic D et al. Growth hormone secretagogues: clinical experience and perspectives. Pediatr Endocrinol Rev. 2008;5 Suppl 2:786-795. PubMed
