Chemical Identity

Property	Value
Examples	GHRP-6, GHRP-2 (Pralmorelin), Hexarelin
Peptide Class	Synthetic Hexapeptides
Receptor	Ghrelin receptor (GHS-R1a)
Route	SC, IV, intranasal

Structure

Growth hormone releasing peptides (GHRPs) are synthetic hexapeptides that stimulate GH release through a mechanism distinct from GHRH. GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) was the first member, followed by GHRP-2 and hexarelin with improved potency and oral activity.

Mechanism of Action

GHRPs bind the growth hormone secretagogue receptor (GHS-R1a, the ghrelin receptor) on pituitary somatotrophs and hypothalamic neurons. This activates phospholipase C/IP3/calcium signaling, synergizing with GHRH to amplify GH release. They also stimulate appetite through hypothalamic pathways.

Clinical Applications

• GH deficiency: Diagnostic stimulation testing
• Body composition: Investigational for muscle wasting
• Appetite stimulation: Ghrelin receptor activation
• Cardiac protection: Hexarelin cardioprotective effects
• Sports doping: Prohibited by WADA

Pharmacology

• GHRP-6: First generation, moderate potency
• GHRP-2 (Pralmorelin): 2-3x more potent than GHRP-6
• Hexarelin: Most potent, some tachyphylaxis
• Synergy: 10x amplification with GHRH co-administration

Safety and Side Effects

Hunger (most common), flushing, cortisol and prolactin elevation (mild), water retention, and joint pain. Long-term safety data limited. Prohibited in athletic competition.

References

• Bowers, C.Y., et al. (1995). GH-releasing peptides. Endocrine Reviews, 16, 63-82.
• Ghigo, E., et al. (1999). GHRPs: mechanism of action. Growth Hormone & IGF Research, 9, 12-17.