GHRH (growth hormone-releasing hormone) is a 44-amino-acid peptide released in pulses from the hypothalamic arcuate nucleus. It reaches the anterior pituitary through the hypophyseal portal circulation and binds GHRHR, a class B GPCR on somatotroph cells, raising cAMP and triggering growth hormone synthesis and release.
Why analogs stop at residue 29
Biological activity resides in the N-terminal fragment: GHRH(1-29), known as sermorelin, retains essentially full potency. Native GHRH is cleaved rapidly by DPP-4 at the Ala2 position, giving a plasma half-life of only a few minutes, so research analogs modify that site. CJC-1295 without DAC (Mod GRF 1-29) carries four substitutions that resist DPP-4 and trypsin, while Tesamorelin adds a trans-3-hexenoyl group to the N-terminus of the full 44-residue sequence.
Why it matters
GHRH analogs act upstream, on the pituitary, so the release they evoke remains pulsatile and subject to somatostatin feedback — a mechanistically different starting point from exogenous growth hormone. In published work they are frequently studied together with a GHRP, because the two act through separate receptors.
Related terms
growth hormone secretagogue · IGF-1. Browse GHRH analogs, see Sermorelin, or compare in Tesamorelin vs Sermorelin.