Mechanism of Action
CJC-1295 No DAC is a synthetic analogue of GHRH(1-29), modified at four amino acid positions to resist DPP-IV enzymatic cleavage. It selectively binds the GHRH receptor on pituitary somatotroph cells, stimulating intracellular cAMP via Gαs-coupled signaling and driving pulsatile growth hormone (GH) secretion.
Ipamorelin acts via selective agonism of GHS-R1a (ghrelin receptor) through a Gαq-coupled IP3/DAG pathway, independent of the GHRH receptor. Noted in research for minimal effect on cortisol and prolactin secretion compared to earlier GH secretagogues.
When studied in combination, the two peptides produce additive or synergistic GH secretory responses by engaging both the GHRH-axis and ghrelin-axis simultaneously. Downstream, GH drives hepatic IGF-1 production via JAK2-STAT5 signaling, with IGF-1 acting through the IGF-1R/PI3K/Akt/mTOR pathway.