Both classes raise growth hormone, but through genuinely different receptor pathways. GHRH analogues like CJC-1295 and Sermorelin bind the GHRH receptor on pituitary somatotrophs, triggering GH release through a cAMP-dependent pathway — essentially mimicking the body's own growth-hormone-releasing hormone.
GHRPs (growth hormone releasing peptides) like Ipamorelin and GHRP-6 work through an entirely separate receptor, the ghrelin receptor (GHS-R1a), amplifying GH release through a calcium-dependent signalling pathway. Ipamorelin is considered the most selective compound in this class, stimulating GH release with minimal effect on cortisol, prolactin, or appetite compared to older GHRPs.
Because the two pathways don't compete for the same receptor, research combining a GHRH analogue with a GHRP (such as CJC-1295 with Ipamorelin) has demonstrated a synergistic effect — a GH response measurably greater than either compound alone — which is the pharmacological rationale behind most GH-secretagogue stacking protocols.
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