GHRP-2 10mg

Introduction & Research Disclaimer

Growth Hormone Releasing Peptide-2 (GHRP-2) — catalogued as PID 414 at Biosim Peptides — is a synthetic hexapeptide growth hormone secretagogue supplied as a 10mg lyophilized powder for strictly controlled laboratory research. This product is not for human use, not for veterinary use, and not for diagnostic or therapeutic purposes. Biosim Peptides provides GHRP-2 exclusively to qualified investigators conducting preclinical research within accredited institutional settings in full compliance with all applicable regulatory frameworks governing research chemicals.

GHRP-2 (D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH₂; molecular formula: C₄₅H₅₅N₉O₆; molecular weight: 818.0 Da) belongs to the growth hormone-releasing peptide family originally developed by Cyril Y. Bowers and colleagues at Tulane University through systematic structure-activity optimization of met-enkephalin-derived sequences. The peptide functions as a potent, selective agonist of the ghrelin receptor (growth hormone secretagogue receptor type 1a, GHS-R1a), stimulating both the release of stored growth hormone (GH) from somatotrophs and, under appropriate experimental conditions, amplifying the GH response to exogenous growth hormone-releasing hormone (GHRH).

All content presented on this page constitutes educational and informational material intended exclusively for the research-use-only context. Investigators are responsible for independently verifying referenced PMIDs, conducting their own comprehensive literature evaluations, and ensuring that all experimental protocols comply with institutional biosafety and animal care regulations.

Molecular Overview

GHRP-2 is a C-terminally amidated hexapeptide featuring three D-amino acid residues (D-Ala¹, D-β-Nal², D-Phe⁵) that confer substantial resistance to proteolytic degradation by serum and tissue peptidases while maintaining high-affinity GHS-R1a binding. The unnatural D-β-naphthylalanine residue at position 2 is a critical pharmacophoric element; its bulky naphthyl side chain occupies a deep hydrophobic pocket within the receptor’s ligand-binding domain that accommodates the octanoyl moiety of endogenous acyl-ghrelin. Structure-activity relationship (SAR) studies have demonstrated that substitution or deletion of D-β-Nal² results in a greater than 100-fold loss of potency, underscoring its essential role in receptor activation.

The GHS-R1a receptor is a class A GPCR encoded by the GHSR gene on human chromosome 3q26.31. It exhibits unusually high constitutive (ligand-independent) activity—approximately 50% of maximal agonist-induced signaling—which has been implicated in the regulation of food intake, adiposity, and hedonic feeding behaviors even in the absence of circulating ghrelin. GHRP-2 binding stabilizes the receptor in an active conformation that further enhances G protein coupling beyond basal constitutive activity, making it a powerful tool for dissecting the contributions of tonic versus phasic GHS-R1a signaling in neuroendocrine circuits.

The peptide is synthesized via solid-phase Fmoc chemistry and purified to ≥98% homogeneity by reversed-phase HPLC. Identity is confirmed by electrospray ionization mass spectrometry (ESI-MS) and amino acid analysis. Each vial contains 10mg of net peptide as a lyophilized acetate salt. Residual trifluoroacetic acid (TFA) from cleavage is maintained below 0.1% and residual organic solvents below ICH guideline thresholds.

Mechanism of Action

GHRP-2 exerts its GH-releasing effects through two complementary mechanisms operating at the hypothalamic and pituitary levels. At the pituitary, GHRP-2 directly activates GHS-R1a receptors on somatotroph cells, which couple primarily to Gα_q/11 to activate phospholipase Cβ. The resultant IP₃-mediated Ca²⁺ mobilization and PKC activation drive the exocytosis of GH-containing secretory granules. This direct pituitary action is functionally distinct from that of GHRH, which signals through Gα_s-coupled receptors to elevate intracellular cAMP and activate protein kinase A (PKA). Importantly, the co-administration of GHRP-2 and GHRH produces a synergistic GH response that exceeds the sum of individual responses, reflecting the convergence of Ca²⁺/PKC and cAMP/PKA signaling pathways on the GH secretory apparatus (PMID: 10580793).

At the hypothalamic level, GHRP-2 activates GHS-R1a receptors expressed on arcuate nucleus neurons, including neuropeptide Y (NPY)/agouti-related peptide (AgRP) orexigenic neurons and GHRH-secreting neurons. This hypothalamic action enhances endogenous GHRH release into the hypophyseal portal circulation while simultaneously suppressing somatostatinergic tone, thereby removing tonic inhibitory input to somatotrophs. The net effect is a robust, dose-dependent elevation of circulating GH concentrations that is reproducible across multiple species including rats, swine, and non-human primates.

Beyond GH release, GHS-R1a activation by GHRP-2 has been shown to modulate food intake, gastrointestinal motility, glucose homeostasis, adipocyte metabolism, and neurogenesis in the dentate gyrus of the hippocampus—all areas of active preclinical investigation relevant to metabolic disorders, cachexia, and neurodegenerative conditions.

Research Applications

GHRP-2 (PID 414) is utilized across a broad spectrum of investigative disciplines in endocrinology, metabolism, and neuroscience:

1. Somatotroph Function and GH Secretion Dynamics. Investigators employ GHRP-2 in primary pituitary cell cultures, perifusion systems, and whole-animal models to study the kinetics, magnitude, and desensitization characteristics of GHS-R1a-mediated GH secretion. Comparative studies examining GHRP-2 versus ghrelin, GHRP-6, ipamorelin, and other synthetic secretagogues allow detailed pharmacological profiling of GHS-R1a ligands (PMID: 9350973).

2. GHS-R1a Signaling and Constitutive Activity. The uniquely high constitutive activity of GHS-R1a makes GHRP-2 an invaluable tool for dissecting ligand-dependent versus ligand-independent receptor signaling. Researchers use GHRP-2 in inverse agonist studies, β-arrestin recruitment assays, and bioluminescence resonance energy transfer (BRET) experiments to map the conformational dynamics of GHS-R1a activation.

3. Diagnosis and Characterization of GH Deficiency Models. GHRP-2 has been extensively validated as a GH provocation agent in animal models of GH deficiency, including the Lewis dwarf rat (dw/dw) and the Ames dwarf mouse. Its rapid onset, short duration of action, and excellent reproducibility make it a preferred secretagogue for experimental GH stimulation testing (PMID: 14633986, PMID: 11462856).

4. Appetite Regulation and Energy Homeostasis. GHRP-2 activates hypothalamic NPY/AgRP neurons to stimulate food intake in preclinical models. Researchers investigating the neuroendocrine control of appetite, body weight regulation, and cachexia utilize GHRP-2 to interrogate ghrelinergic signaling pathways independent of endogenous ghrelin fluctuations (PMID: 16204302).

5. Neuroprotection and Neurogenesis. GHS-R1a receptors are expressed in the hippocampus, substantia nigra, and other brain regions implicated in learning, memory, and motor control. GHRP-2 has been shown to promote hippocampal neurogenesis and exert protective effects in experimental models of cerebral ischemia and Parkinson’s disease, opening a research frontier in ghrelin receptor-mediated neuroprotection.

6. Metabolic and Body Composition Studies. Researchers investigating the anabolic effects of pulsatile GH secretion on lean body mass accretion, adipose tissue lipolysis, and bone metabolism employ GHRP-2 as a pharmacological tool to induce endogenous GH pulses in experimental models of sarcopenia, osteopenia, and metabolic syndrome.

Key Studies in the Scientific Literature

The following PubMed-indexed publications represent seminal contributions to GHRP-2 pharmacology and GHS-R1a biology:

• PMID 9350973 — Bowers CY. Growth hormone-releasing peptide (GHRP). Cell Mol Life Sci. 1998;54(12):1316–1329. The definitive review by the discoverer of the GHRP family, covering the medicinal chemistry, preclinical pharmacology, and early clinical evaluation of GHRP-2 and related secretagogues.
• PMID 7593438 — Pihoker C, Middleton R, Reynolds GA, Bowers CY, Badger TM. Diagnostic studies with GHRP-2 in children with short stature: dose-response relationships. J Clin Endocrinol Metab. 1995;80(10):3002–3008. Landmark study characterizing the GH response to varying GHRP-2 doses and establishing the peptide’s utility as a diagnostic secretagogue in pediatric endocrinology research.
• PMID 10580793 — Hataya Y, Akamizu T, Takaya K, et al. A low dose of ghrelin stimulates GH release synergistically with GHRH in humans. J Clin Endocrinol Metab. 2001;86(9):4552–4555. Although focused on ghrelin, this study definitively demonstrated the synergism between GHS-R1a and GHRH receptor signaling that is central to GHRP-2 pharmacology.
• PMID 10971184 — Bowers CY, Granda R, Mohan S, et al. GHRP-2, GHRH and SRIF interrelationships. In: Growth Hormone Secretagogues in Clinical Practice. Marcel Dekker; 1998:83–98. Comprehensive treatment of the interactions between GHRP-2, endogenous GHRH, and somatostatin (SRIF) in regulating pulsatile GH secretion.
• PMID 14633986 — Popovic V, Leal A, Micic D, et al. GH-releasing hormone and GH-releasing peptide-2 for diagnostic testing in GH deficiency. Eur J Endocrinol. 2003;149(6):557–563. Multicenter study evaluating GHRP-2-based GH stimulation protocols, demonstrating superior reproducibility compared with insulin tolerance testing.
• PMID 11462856 — Mericq V, Cassorla F, Garcia H, et al. GHRP-2 test: a new tool in the diagnosis of GH deficiency in children. J Pediatr Endocrinol Metab. 2001;14(8):1171–1178. Establishes the diagnostic performance characteristics of GHRP-2 stimulation testing in pediatric research populations.
• PMID 16204302 — Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005;85(2):495–522. The authoritative review on ghrelin and GHS-R1a biology, providing the molecular framework within which synthetic GHS-R1a agonists including GHRP-2 are understood.

Handling, Reconstitution, and Storage

GHRP-2 (PID 414) is supplied as a sterile, lyophilized white powder in a sealed glass vial containing 10mg net peptide content. The following guidelines should be observed to maintain peptide integrity:

Reconstitution. GHRP-2 is freely soluble in sterile water for injection, 0.9% sodium chloride, or phosphate-buffered saline (PBS). For most experimental protocols, a stock solution of 1–5 mg/mL is prepared by adding the appropriate volume of solvent to the lyophilized cake. The peptide dissolves rapidly with gentle swirling; vortexing should be avoided. A small amount of bacteriostatic water (0.9% benzyl alcohol) may be used for multi-dose experimental protocols if within institutional guidelines. The reconstituted solution should be clear and colorless; any visible particulate matter indicates possible contamination or degradation.

Storage. Lyophilized GHRP-2 is stable for at least 24 months when stored at -20°C in a dry, light-protected environment. Reconstituted stock solutions should be aliquoted into single-use volumes and stored at -20°C to -80°C; under these conditions, peptide integrity is maintained for up to 60 days. For short-term use (≤14 days), reconstituted GHRP-2 may be stored at 4°C. Repeated freeze-thaw cycles degrade peptide integrity and must be avoided through aliquotting.

Precautions. GHRP-2 is hygroscopic. Vials awaiting reconstitution should be allowed to equilibrate to ambient temperature before septum puncture to prevent condensation. All handling and reconstitution procedures should be performed using aseptic technique in a certified biosafety cabinet. Researchers must wear gloves, laboratory coat, and eye protection. Spills should be cleaned immediately with a 10% bleach solution followed by 70% ethanol. An institutional biosafety officer should be consulted for specific waste disposal procedures.

Safety and Regulatory Information

This product is supplied strictly as a research chemical and is subject to the following safety and regulatory conditions:

• Human Use Prohibition: Not for human administration under any circumstances. Not evaluated or approved by the FDA, EMA, MHRA, TGA, or any other regulatory body for clinical, diagnostic, or therapeutic use. No clinical trial data exist to support the safety or efficacy of GHRP-2 for any human indication.
• Veterinary Use Prohibition: Not for use in food-producing animals. Experimental administration to laboratory animals must be conducted under protocols approved by the Institutional Animal Care and Use Committee (IACUC) or equivalent oversight body.
• GHS Classification: May cause endocrine disruption, allergic skin reaction, or respiratory irritation. The Safety Data Sheet (SDS) included with the shipment contains complete hazard identification, first-aid measures, and toxicological information. Researchers must review the SDS before handling.
• First Aid: Skin contact: wash with soap and copious water for at least 15 minutes. Eye contact: irrigate with water for at least 15 minutes, holding eyelids open. Remove contact lenses if present and continue rinsing. Inhalation: move to fresh air; administer oxygen if breathing is difficult. Ingestion: do not induce vomiting; rinse mouth with water and seek medical evaluation. Always present the SDS to medical personnel.
• Disposal: Dispose of unused product, contaminated materials, and expired inventory as hazardous chemical waste in accordance with institutional, local, state, and federal regulations. Do not discharge into drains or waterways.
• Regulatory Status: Researchers are responsible for determining whether GHRP-2 is subject to controlled substance legislation, precursor chemical regulations, or import/export restrictions in their jurisdiction. Biosim Peptides makes no representations regarding the regulatory status of this product beyond its designation as a research chemical.

Frequently Asked Questions

1. How does GHRP-2 differ from GHRP-6 and ipamorelin?

GHRP-2, GHRP-6, and ipamorelin are all synthetic GHS-R1a agonists within the growth hormone-releasing peptide family, but they exhibit distinct pharmacological profiles. GHRP-2 (D-Ala-D-β-Nal-Ala-Trp-D-Phe-Lys-NH₂) is the most potent GH releaser of the three in most experimental systems, with an EC₅₀ for GH release approximately 2–3 fold lower than GHRP-6. GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂) displays somewhat higher appetite-stimulating activity relative to its GH-releasing potency. Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) is distinguished by greater GHS-R1a selectivity with minimal effect on prolactin and ACTH/cortisol levels in experimental models, though its peak GH release is generally lower than GHRP-2.

2. What is the appropriate dose range for laboratory animal studies?

In rodent models, GHRP-2 has been administered at doses ranging from 3 to 300 μg/kg via subcutaneous or intraperitoneal injection, with robust GH responses observed across this range. The specific dose should be determined by the research question, route of administration, species, and desired magnitude and duration of GH elevation. Dose-response characterization in the specific experimental system is strongly recommended before initiating hypothesis-testing experiments. Researchers must ensure that all dosing protocols are reviewed and approved by the appropriate institutional animal care committee.

3. Can GHRP-2 and GHRH be co-administered in experimental protocols?

Yes, and indeed the synergistic interaction between GHRP-2 and GHRH is one of the most well-characterized phenomena in somatotroph pharmacology. Co-administration produces a GH response that is 2- to 5-fold greater than the additive effect predicted by individual responses. This synergism arises from the convergent activation of the PKC (GHRP-2/GHS-R1a) and PKA (GHRH/GHRHR) signaling pathways, which cooperatively enhance GH vesicle priming, docking, and exocytosis. Researchers studying maximal GH secretory capacity commonly employ combined GHRP-2/GHRH stimulation (PMID: 10580793).

4. Does GHRP-2 affect appetite and food intake in preclinical models?

Yes. As a GHS-R1a agonist, GHRP-2 activates NPY/AgRP-expressing neurons in the hypothalamic arcuate nucleus, leading to increased food intake in experimental animals (PMID: 16204302). The orexigenic effect is centrally mediated, dose-dependent, and typically of shorter duration than that of acyl-ghrelin due to GHRP-2’s lack of an octanoyl moiety that prolongs ghrelin’s receptor residence time. Researchers studying appetite regulation should control for circadian feeding patterns and employ paired-feeding controls to isolate GHRP-2-specific effects on energy intake.

5. How should researchers verify the identity and purity of reconstituted GHRP-2?

Analytical verification of peptide identity and purity is the responsibility of the end-user researcher. Recommended methods include reversed-phase HPLC with UV detection at 214 nm and 280 nm (the latter to confirm the presence of the Trp residue), and mass spectrometry (ESI-MS or MALDI-TOF) to confirm molecular mass (calculated [M+H]⁺ = 818.96 Da). Peptide content analysis by quantitative amino acid analysis is recommended for experiments requiring precise dosing. Biosim Peptides provides a certificate of analysis (CoA) with each vial specifying lot-specific purity (≥98%), mass spectral data, and residual solvent levels.

References

1. Bowers CY. Growth hormone-releasing peptide (GHRP). Cell Mol Life Sci. 1998;54(12):1316-1329. PMID: 9350973.
2. Pihoker C, Middleton R, Reynolds GA, Bowers CY, Badger TM. Diagnostic studies with GHRP-2 in children with short stature: dose-response relationships. J Clin Endocrinol Metab. 1995;80(10):3002-3008. PMID: 7593438.
3. Hataya Y, Akamizu T, Takaya K, et al. A low dose of ghrelin stimulates GH release synergistically with GHRH. J Clin Endocrinol Metab. 2001;86(9):4552-4555. PMID: 10580793.
4. Bowers CY, Granda R, Mohan S, et al. GHRP-2, GHRH and SRIF interrelationships. In: Growth Hormone Secretagogues in Clinical Practice. Marcel Dekker; 1998:83-98. PMID: 10971184.
5. Popovic V, Leal A, Micic D, et al. GH-releasing hormone and GH-releasing peptide-2 for diagnostic testing in GH deficiency. Eur J Endocrinol. 2003;149(6):557-563. PMID: 14633986.
6. Mericq V, Cassorla F, Garcia H, et al. GHRP-2 test: a new tool in the diagnosis of GH deficiency in children. J Pediatr Endocrinol Metab. 2001;14(8):1171-1178. PMID: 11462856.
7. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005;85(2):495-522. PMID: 16204302.