GHRH Analogues and Ghrelin-Receptor Agonists

The GHRH receptor is a class B GPCR on pituitary somatotrophs that signals through Gs and cAMP. Sermorelin is GHRH(1-29) amide, the shortest fully active fragment of the 44-residue hormone. CJC-1295 is a modified GHRH(1-29) with four substitutions that resist enzymatic cleavage; the DAC version adds a lysine-linked maleimide that binds serum albumin covalently. Tesamorelin is GHRH(1-44) with an N-terminal trans-3-hexenoyl group. GHS-R1a is a class A GPCR coupled mainly to Gq and calcium signalling. Its peptide agonists (GHRP-2, GHRP-6, hexarelin, ipamorelin) are short synthetic sequences rich in D-amino acids, and non-peptide agonists of the same receptor also exist.

IGF-1 LR3 is an 83-residue analogue of insulin-like growth factor 1 with an N-terminal extension and an arginine substitution at position 3 that lowers binding to IGF binding proteins. MGF and PEG-MGF are peptides derived from an alternatively spliced IGF-1 E-domain. Recombinant human growth hormone is the 191-residue, 22 kDa protein. None of these acts at the GHRH receptor or GHS-R1a; they are grouped here only because they appear beside the secretagogues in supplier catalogues.

Identity is established by mass spectrometry: an intact mass, or a precursor and fragment transition (MRM) matched against a reference standard, confirms that the sequence in the vial is the one on the label. Purity is a chromatographic figure, the principal peak area by reversed-phase HPLC, and it bounds peptide-related impurities only; it says nothing about counterion, water or residual solvent content, which is why net peptide content is reported separately. Lyophilised material is stored cold, dry and dark, and a certificate states what was measured on one named lot. For the GHRH analogues, deamidation and oxidation products elute close to the main peak and are the impurities to look for. For CJC-1295 with DAC the reactive maleimide group makes the intact mass and its stability in solution particularly important to confirm.

In vitro work on this class measures receptor activation (cAMP for the GHRH receptor, calcium flux or IP-1 accumulation for GHS-R1a), receptor selectivity, and hormone secretion from cultured pituitary cells. Ghrelin-receptor agonists differ in selectivity: some also stimulate ACTH or prolactin release in cell and animal models, which is the comparison researchers most often make between them. Much of the older literature comes from a small number of laboratories, so check whether a finding has been reproduced independently.