GRF (sermorelin), CJC 1295 w/o DAC (mod GRF), and CJC with DAC are all extremely popular growth hormone related peptides, all of which are frequently used in research settings. At the core, each of these peptides share a similar function, as they are all essentially mimicking Growth Hormone Releasing Hormone (GHRH), a hormone which stimulates pituitary growth hormone release.
Alongside their popularity has been controversy, as throngs of peptide researchers debate the differences between these relatively similar compounds and argue for the efficacy of one over the other. The purpose of this article will be to explain the specifics of each compound and illustrate their differences, with the hope of allowing researchers to better select which of these GHRH agonists is appropriate for their specific studies.
Growth is the most similar to GHRH of all of the three peptides discussed in this article. While Growth Hormone Releasing Hormone contains a 44 amino acid long peptide chain, only 29 of these amino acids are essential to the endocrine function of GHRH. GRF is a match of these 29 amino acids. Administration of GRF is expected to produce effects seen in GHRH, such as elevated IGF-1, elevated serum GH, and deep-wave sleep initiation.
The same bioidentical nature that makes GRF appealing is also the cause of its greatest drawback. GHRH, by nature, has a short half-life. This short half-life is responsible for the pulsatile nature of growth hormone release, as GHRH is destroyed biologically shortly after it is released. Similarly, GRF has only an 11-12 minute half-life in subjects[i]. This short half-life means that, while GRF will be nearly identical to GHRH, the effects will be largely limited and therefore may present some research complications such as the need for frequent administration.
CJC 1295 w/o DAC (mod GRF)
Mod GRF is the answer to the problem of short half-life observed in Sermorelin. Researchers noted the need for a GRF that would similarly mimic GHRH but provide a longer active life before breakdown. This was accomplished by rearranging the amino acids in GRF enough to delay the break down and extend the half-life by bioconjugating the peptide to serum albumin. This extended the half-life to roughly 30min[ii], nearly double that of its predecessor Sermorelin.
CJC 1295 with DAC
The discovery of modified GRF lead to the discovery of the next generation of GHRH agonists: CJC 1295 with DAC). While the extended half-life of 30min in Mod GRF was an improvement over Sermorelin, researchers recognized the potential to make a truly long acting GHRH agonist. The addition of Drug Affinity Complex (DAC) allows CJC 1295 to bind to albumin in such a way that it is very difficult for peptide degradation to occur. The half-life of CJC 1295 with DAC is estimated around 5-8 days[iii].
The greatest concern surrounding the research use of CJC 1295 with DAC is the prolonged half-life will destroy the bioidentical nature of the peptide and render is not a true GHRH agonist. The concern here is that CJC 1295 with DAC will induce a “bleed” of GH in research subjects, which is contrary to the pulsatile manner in which GH is released. If true, this would render CJC 1295 with DAC a poor choice for researchers looking to research the effects of GHRH. Fortunately, researchers have found that even under the conditions of the extended half-life, subjects retain their regular pulsatile secretion of GH. While GH is released in the same manner as it would be under any normal condition, serum levels of GH and IGF rise markedly in subjects undergoing CJC 1295 with DAC administration.
Sermorelin Acetate (Sermorelin) Drug Information: Clinical Pharmacology – Prescribing Information at RxList (RxList)
Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog