GHRP-2 (Growth Hormone Releasing Peptide-2) is a synthetic hexapeptide that functions as a potent growth hormone secretagogue. This peptide belongs to the class of growth hormone releasing peptides (GHRPs) and operates by mimicking the action of ghrelin, the endogenous hunger hormone. GHRP-2 was developed as an investigational compound to stimulate growth hormone release through novel receptor pathways distinct from traditional growth hormone-releasing hormone (GHRH) mechanisms.
The peptide sequence of GHRP-2 consists of six amino acids with the formula D-Ala-D-(β-naphthyl)-Ala-Trp-D-Phe-Lys-NH2. Commercially known as pralmorelin (INN) or by developmental codes KP-102 and GPA-748, GHRP-2 has undergone extensive clinical evaluation and is marketed in Japan as GHRP Kaken 100 for diagnostic assessment of growth hormone deficiency.
Mechanism of Action
GHRP-2 functions primarily through the ghrelin receptor (GHS-R1a), which is located in both the hypothalamus and anterior pituitary gland. When administered, GHRP-2 binds to the growth hormone secretagogue receptor and stimulates the release of growth hormone from the anterior pituitary gland. This mechanism operates independently from the GHRH pathway, providing an alternative route for growth hormone stimulation.
Research published in PubMed demonstrates that GHRP-2 stimulates GH secretion from bovine pituitary cells through multiple pathways, including:
- Calcium influx via calcium channels
- Protein kinase C pathway activation
- Cyclic AMP (cAMP) pathway stimulation
- Partial interaction with GRF receptors
The peptide also exhibits ghrelin-like properties by increasing food intake in healthy men, indicating its dual role in both growth hormone regulation and appetite stimulation. This dual action profile distinguishes GHRP-2 from other growth hormone secretagogues that may not possess significant appetite-stimulating properties.
Clinical Applications and Research
Growth Hormone Deficiency
Clinical studies have established GHRP-2’s efficacy in treating growth hormone deficiency. Research published in The Journal of Clinical Endocrinology & Metabolism demonstrated that eight months of treatment with graded doses of GHRP-2 in GH-deficient children resulted in improved growth velocity compared to pretreatment and post-treatment evaluations. However, the study noted that serum levels of IGF-I and IGFBP-3 did not increase significantly, and the effect of GHRP-2 injections was relatively brief.
Critical Illness Applications
Advanced clinical research has explored GHRP-2’s potential in critically ill patients. Studies published in PubMed revealed that combined administration of GHRP-2 with TRH and GnRH to men with prolonged critical illness evoked superior endocrine and metabolic effects compared to GHRP-2 treatment alone. This combination therapy successfully reactivated the GH, TSH, and LH axes in prolonged critically ill men and produced beneficial metabolic effects absent with single-agent therapy.
Animal Model Research
Veterinary research has provided valuable insights into GHRP-2’s mechanism and efficacy. Studies in swine published in ScienceDirect demonstrated that GHRP-2 stimulates GH release and enhances growth performance in swine, representing the first investigation to assess the in vivo potency of GHRP-2 in eliciting GH release and enhancing growth performance in this species.
Dosage and Administration
Clinical Dosing Protocols
Research-based dosing protocols vary depending on the intended application and route of administration. Clinical studies utilizing subcutaneous infusion employed doses of 1 microgram per kilogram per hour for 270-minute infusions in healthy males, with no adverse side effects reported. This dosing protocol has been validated as safe for acute administration.
Pediatric Applications
Oral administration studies in children have demonstrated bioactivity at doses of 300 micrograms per kilogram body weight, confirming the peptide’s oral bioavailability. Twelve-month oral administration protocols have been established as safe in pediatric populations.
Adult Dosing Considerations
Current dosing recommendations from specialized peptide sources suggest moderate dosing protocols of 100-150 micrograms per dose, administered 2-3 times daily. This dosing range balances efficacy with minimization of potential side effects, particularly appetite stimulation and minor hormonal fluctuations.
Pharmacokinetics and Bioavailability
GHRP-2 demonstrates remarkable versatility in administration routes. Research confirms effectiveness via intravenous, oral, and intranasal administration, making it one of the most versatile members of the GHRP family. The peptide’s oral bioactivity has been documented across multiple species, with studies in goats confirming activity at doses of 5-10 mg/kg body weight.
The peptide exhibits rapid onset of action with relatively brief duration effects. Growth hormone profiles show that GHRP-2 injections produce relatively brief effects, with little impact on GH secretion later in the night, indicating the need for multiple daily administrations for sustained effects.
Safety Profile and Side Effects
Short-term Safety
Extensive safety data supports GHRP-2’s favorable tolerability profile. Clinical studies document that subcutaneous infusion of GHRP-2 for 270 minutes is safe, with no adverse side effects reported during 30-day continuous subcutaneous infusion protocols or 12-month oral administration in children.
Long-term Considerations
Chronic GHRP use may influence prolactin and ACTH levels, requiring monitoring in extended treatment protocols. The peptide’s appetite-stimulating properties, while beneficial in certain therapeutic contexts, may require management in populations where weight gain is undesirable.
Hormonal Effects
GHRP-2 produces mild stimulatory effects on prolactin, ACTH, and cortisol levels in addition to its primary growth hormone-releasing activity. These effects are generally considered minor but warrant consideration in comprehensive treatment planning.
Comparative Analysis with Other Peptides
Potency Comparisons
GHRP-2 demonstrates superior potency compared to GHRP-6 and exhibits stronger GH stimulation than ipamorelin, though with more pronounced appetite stimulation. Unlike MK-677, GHRP-2 does not produce sustained 24-hour GH elevation but works effectively in pulsatile combination protocols.
Synergistic Applications
Research published in Neuroendocrinology demonstrates that GHRP-2 exhibits synergistic action when combined with GHRH analogues, making it particularly valuable in combination therapy protocols. This synergistic effect enhances overall growth hormone release beyond what either compound achieves individually.
Research Applications and Future Directions
Cytoprotective Properties
Historical research documents indicate that GHRP-2 belongs to a family of peptidyl growth hormone secretagogues with broad cytoprotective properties. These properties extend beyond simple growth hormone release, suggesting potential applications in cellular protection and tissue repair.
Metabolic Research
Current research explores GHRP-2’s role in hormone, metabolism, and growth studies, particularly when combined with Modified GRF 1-29. These combination studies investigate synergistic impacts on metabolic parameters and growth factor regulation.
Regulatory Status and Commercial Availability
GHRP-2 maintains regulatory approval in Japan under the brand name GHRP Kaken 100 for diagnostic assessment of growth hormone deficiency. In other jurisdictions, the compound remains primarily available for research purposes. The peptide’s established safety profile and documented efficacy support its continued investigation in various therapeutic applications.
Conclusion
GHRP-2 represents a significant advancement in growth hormone secretagogue technology, offering potent GH-releasing activity through novel receptor pathways. Its demonstrated safety profile, multiple administration routes, and synergistic potential with other peptides establish it as a valuable tool in both clinical and research applications. The compound’s dual role in growth hormone stimulation and appetite regulation provides unique therapeutic opportunities, while its established pharmacokinetic profile supports flexible dosing protocols across diverse patient populations.
The extensive clinical database supporting GHRP-2’s safety and efficacy, combined with its regulatory approval for diagnostic applications, positions this peptide as a cornerstone compound in growth hormone research and therapy. Future research directions continue to explore its cytoprotective properties and metabolic effects, potentially expanding its therapeutic applications beyond traditional growth hormone deficiency treatment.