GHRP-2

GHRP‑2

Overview

GHRP‑2 (growth hormone‑releasing peptide‑2, pralmorelin) is a synthetic hexapeptide and high‑affinity agonist of the ghrelin receptor (GHS‑R1a). It is one of the best‑characterized growth hormone secretagogues and has been extensively used as:

• A diagnostic test agent for growth hormone deficiency
• A tool compound to interrogate GH/IGF‑1 axis physiology
• A probe for ghrelin‑receptor–mediated effects in muscle, cardiovascular, immune, sleep, and pain pathways

GHRP‑2 is active after oral, sublingual, and parenteral administration in human and animal studies, making it a versatile research molecule for pharmacokinetic and pharmacodynamic investigations.

Chemical and Structural Information

• Name: GHRP‑2 (Pralmorelin)
• Peptide sequence: H–D‑Ala–D‑2‑Nal–Ala–Trp–D‑Phe–Lys–NH₂
• Peptide length: Hexapeptide
• Molecular formula: C₄₅H₅₅N₉O₆
• Molecular weight: ~817.0 g/mol
• Receptor target: Ghrelin/GHS‑R1a agonist

Key Research Findings

1. Regulation of Muscle Protein Turnover

• In growth‑retarded yaks, GHRP‑2 improved average daily gain, enhanced somatotropic axis hormone levels, and increased muscle protein deposition .
• In myocyte cell culture, GHRP‑2 directly attenuated the dexamethasone‑induced upregulation of atrogin‑1 and MuRF1, critical mediators of ubiquitin‑proteasome–dependent muscle proteolysis .

These data show that GHRP‑2 exerts dual actions on skeletal muscle:

1. Endocrine: stimulation of GH and consequent IGF‑1 signaling undefined +1
2. Autocrine/paracrine: direct modulation of atrophy‑related genes

Together, these effects make GHRP‑2 a valuable research tool for studying sarcopenia, cachexia, steroid‑induced myopathy, and growth retardation in animal models.

2. Orexigenic Effects and Energy Balance

Acute administration of GHRP‑2 in human volunteers:

• Significantly increases caloric intake and hunger ratings in healthy men
• Produces a similar orexigenic response in obese subjects, who maintain sensitivity to ghrelin agonism

This positions GHRP‑2 as a key reference compound for:

• Dissecting central and peripheral mechanisms of appetite control
• Modelling hyperphagia and energy surplus
• Evaluating ghrelin pathway modulation in obesity and metabolic research

3. Cardiovascular and Mitochondrial Effects

Work in animal and cellular systems has revealed that GHRP‑2:

• Reduces cardiomyocyte apoptosis and exerts anti‑ischemic and cardioprotective effects, likely via mitochondrial stabilization
• Interacts with specific cardiac receptors for growth hormone‑releasing peptides, distinct from pituitary GHS‑R, broadening the receptor map for this peptide family

These discoveries support the use of GHRP‑2 in studies of heart failure, ischemia–reperfusion injury, and cardiometabolic signaling pathways.

4. Thymic Function and Immune Modulation

Ghrelin receptor agonists, including GHRP‑2, have been implicated in:

• Mitigating age‑related thymic involution
• Increasing thymic output and expanding T‑cell diversity, which are crucial for robust adaptive immunity

GHRP‑2 thus provides a mechanistic link between endocrine control and immune senescence, making it useful for models of immunosenescence, infection, and tumor immunosurveillance.

5. Sleep and Neuroendocrine Integration

The growth hormone secretagogue MK‑677 has been shown to:

• Enhance deep slow‑wave sleep (stages 3–4)
• Improve overall sleep quality in human subjects

While these data are derived from MK‑677, not GHRP‑2 specifically, they underscore the broader role of GHS‑R agonism in neuroendocrine sleep regulation. GHRP‑2 serves as a complementary tool to explore:

• GH–sleep feedback loops
• Interactions between sleep stages, metabolism, and tissue repair
• The role of ghrelin signaling in circadian physiology

6. Pain Modulation via Opioid Receptors

In mice, supraspinal administration of GHRP‑2:

• Produces robust antinociception in multiple pain paradigms
• Has its analgesic effect reversed by opioid receptor antagonists

This indicates functional cross‑talk between ghrelin receptors and opioid systems. GHRP‑2 is therefore useful for:

• Mapping opioid receptor subtype selectivity
• Evaluating non‑classical pathways for pain modulation
• Exploring strategies for analgesia potentially uncoupled from respiratory depression and classical opioid side effects

Use Limitations and Compliance

• Not approved for any therapeutic, diagnostic, or prophylactic application in humans or animals.
• Not a dietary supplement, cosmetic ingredient, or pharmaceutical product.
• Intended exclusively for controlled laboratory research by qualified professionals.

Any extrapolation from animal or in vitro data to humans is speculative and inappropriate outside of formal research protocols.

Article Author

Prepared and scientifically curated by Dr. Logan, M.D., Case Western Reserve University School of Medicine (M.D.) and B.S. in Molecular Biology.

Scientific Contribution Acknowledgment

Jean‑Alain Fehrentz, Ph.D. is a recognized expert in peptide chemistry and ghrelin receptor ligands, with >100 publications spanning:

• Peptide and peptidomimetic design
• Enzyme inhibition
• Ghrelin receptor pharmacology and growth hormone secretagogues

He is referenced here solely to acknowledge his foundational contributions to GHRP‑2 and related ligands. Dr. Fehrentz does not endorse, sponsor, or have any relationship—direct or implied—with Peptide Sciences or the sale/use of this peptide.

Referenced Citations (v2)

Same as in v1:

1. Hu, R. et al. PLOS ONE. 2016;11(2):e0149461.
2. Yamamoto, D. et al. Life Sci. 2008;82(9–10):460–466.
3. Phung, L.T. et al. Domest. Anim. Endocrinol. 2000;18(3):279–291.
4. Laferrère, B. et al. J. Clin. Endocrinol. Metab. 2005;90(2):611–614.
5. Laferrère, B. et al. Obesity (Silver Spring). 2006;14(6):1056–1063.
6. Muccioli, G. et al. Ann. Endocrinol. (Paris). 2000;61(1):27–31.
7. Bodart, V. et al. Circ. Res. 1999;85(9):796–802.
8. Taub, D.D. et al. Curr. Opin. Pharmacol. 2010;10(4):408–424.
9. Gopinath, G. et al. Neuroendocrinology. 1997;66(4):278–286.
10. Zeng, P. et al. Peptides. 2014;55:103–109.
11. Moulin, A. et al. ChemMedChem. 2007;2:1242–1259.