GHRH Analogs vs. GHRPs: Structural and Receptor Differences

Two families of peptides appear frequently in growth hormone (GH) axis research: growth hormone-releasing hormone (GHRH) analogs and growth hormone-releasing peptides (GHRPs), also called GH secretagogues. They are often discussed together, but they differ in structure and in the receptor they target.

GHRH analogs

Natural GHRH is a 44-amino-acid hypothalamic hormone. It acts on the GHRH receptor (GHRHR), a class B G-protein-coupled receptor on pituitary somatotroph cells. Research analogs are built from its active region:

• Sermorelin, GHRH(1-29), the shortest fully active fragment of natural GHRH.
• Tesamorelin, a full-length GHRH(1-44) analog with an N-terminal trans-3-hexenoyl modification that improves stability.
• CJC-1295 with DAC, a modified GRF(1-29) with a Drug Affinity Complex (DAC). The DAC lets the peptide bind to circulating albumin, which greatly extends its half-life in research models.
• CJC-1295 without DAC, often called Modified GRF(1-29). It has the same stabilizing amino acid substitutions without the albumin-binding group, so its half-life is short.

GHRPs (GH secretagogues)

GHRPs are small synthetic peptides that act on a different receptor: the growth hormone secretagogue receptor (GHS-R1a), the same receptor bound by the hormone ghrelin.

• Ipamorelin is a pentapeptide described in the research literature as the first selective GH secretagogue. Studies reported that it released GH with minimal effect on ACTH and cortisol (Raun et al., 1998).

Why researchers study them together

Because GHRH analogs and GHRPs act through two separate receptors, researchers often study them in combination to examine how the two pathways interact. This is the rationale behind combination products such as CJC-1295 (No DAC) + Ipamorelin.

Summary

	GHRH analogs	GHRPs
Receptor	GHRH receptor (GHRHR)	GHS-R1a (ghrelin receptor)
Typical size	29–44 amino acids	5–7 amino acids
Examples	Sermorelin, Tesamorelin, CJC-1295	Ipamorelin

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References

• Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology, 1998.
• Teichman SL, et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone. Journal of Clinical Endocrinology & Metabolism, 2006.