GHRP-2

GHRP-2 (growth hormone releasing peptide-2), marketed in Japan as pralmorelin (Grelin), is a synthetic hexapeptide GH secretagogue that stimulates pulsatile GH release by activating the ghrelin receptor (GHS-R1a). It is approved in Japan for the diagnosis of GH deficiency and was in Phase 2 development in the United States before Wyeth discontinued the program. GHRP-2 is widely used in research and compounding contexts as a GH secretagogue.

Unlike ipamorelin — which selectively stimulates GH with minimal cortisol/ACTH co-activation — GHRP-2 activates both the GH axis and the HPA axis (ACTH/cortisol) via dual PKA and PKC signaling pathways in pituitary cells. This dual activation makes GHRP-2 useful as a two-in-one diagnostic tool (simultaneous GH + secondary adrenal insufficiency testing) but reduces its selectivity as a GH secretagogue relative to ipamorelin.

GHRP-2 is a full agonist at GHS-R1a (ghrelin receptor), a GPCR expressed on somatotroph and ACTH-secreting cells of the anterior pituitary. Unlike ipamorelin, which activates only Gαq/PKC, GHRP-2 activates both the PKA pathway (cAMP → PKA → GH gene expression) and the PKC pathway (IP3/DAG → Ca²⁺ → exocytosis), resulting in more robust GH pulse but with concurrent ACTH stimulation.

The non-standard amino acids in GHRP-2's sequence confer key properties: - **D-amino acids (D-Ala, D-βNal, D-Phe):** Resist proteolytic degradation, dramatically extending metabolic stability vs. native ghrelin - **β-naphthylalanine (βNal):** Large aromatic ring provides optimal GHS-R1a binding affinity - **C-terminal amide:** Reduces renal clearance and improves receptor engagement

GHRP-2 also shares with ghrelin the capacity to stimulate appetite and gastric motility via GHS-R1a in the hypothalamus and gut, independent of its pituitary GH effects.