GHRP-2

GHRP-2 (Growth Hormone Releasing Peptide-2), also known as pralmorelin, is a synthetic hexapeptide that acts as a potent agonist of the growth hormone secretagogue receptor (GHSR, also known as the ghrelin receptor). Developed in the 1990s by Bowers et al., GHRP-2 was one of the first synthetic GH secretagogues characterized and has been used as a clinical diagnostic agent for GH deficiency assessment in Japan (marketed as GHRP Kaken 100). The peptide contains unnatural amino acids including D-alanine, D-2-naphthylalanine, and D-phenylalanine, which confer resistance to enzymatic degradation. GHRP-2 is considered one of the most potent peptide GHSR agonists, with greater GH-releasing activity than GHRP-6 or hexarelin in comparative studies. It stimulates GH release through a mechanism independent of GHRH, acting directly at the pituitary and hypothalamic levels.

GHRP-2 has been investigated for its agonist activity at the growth hormone secretagogue receptor 1a (GHS-R1a), the same receptor activated by the endogenous hormone ghrelin. Researchers observed that GHSR activation by GHRP-2 triggers Gq-coupled phospholipase C signaling, leading to IP3-mediated calcium release from intracellular stores in pituitary somatotrophs, which triggers GH secretory vesicle exocytosis. Studies suggest that GHRP-2 also acts at the hypothalamic level, stimulating GHRH neurons and suppressing somatostatin release, creating a permissive environment for GH pulse generation. GHRP-2 demonstrates synergistic GH release when combined with GHRH or its analogs, as they act through distinct intracellular signaling cascades (cAMP for GHRH versus calcium/PKC for GHRP-2). In clinical studies, researchers observed dose-dependent GH responses and noted that GHRP-2 produces less appetite stimulation than GHRP-6 despite similar GH-releasing potency.

Clinical GH Stimulation

Bowers et al. (1990) characterized the GH-releasing properties of GHRP-2 and demonstrated its synergistic interaction with GHRH in both animal and human studies, establishing the pharmacological basis for dual secretagogue approaches [1].

Diagnostic Applications

Doi et al. (2004) investigated GHRP-2 as a diagnostic provocative test for GH deficiency. The study established GHRP-2 as a reliable and reproducible GH stimulation agent, leading to its clinical adoption in Japan [2].

Comparative Potency

Bowers CY (1998) reviewed the growth hormone secretagogue peptide family, comparing GHRP-2, GHRP-6, hexarelin, and non-peptide secretagogues. GHRP-2 was characterized as the most potent peptide GHSR agonist with favorable selectivity [3].