Growth Hormone Releasing Hormone (GHRH) is one of the most studied hormonal peptides. Over the last 4 decades lots of analogs have been developed (sermorelin, tesamorelin, CJC-1295) to help scientists understand how the pituitary regulates GH via GHRH. One of the most commonly discussed is MOD GRF 1-29 (Tetrasubstituted GRF 1-29 or CJC-1295 without the DAC)
What is MOD GRF 1-29?
Growth Hormone Releasing Hormone (GHRH) is a 44 amino acid peptide naturally produced by the hypothalamus. It binds to GHRH receptors located on the Somatotroph cells of the anterior pituitary.
Early research using structure activity relationships found that the full molecule was not needed, only the first 29 amino acids (GRF(1-29)NH2) were needed to produce near full biological activity at the receptor. This led to the development of sermorelin, which was originally FDA approved in 1990 (Geref). However the product was discontinued, however in 2013 the FDA stated that it was not discontinued due to concerns around safety or effectiveness.
The problem with this peptide is that it has a very short half life. A study in 1986 looked at the native GHRH peptide and found that it had a very short half-life in vivo due to rapid removal of the first two residues by a plasma dipeptidyl aminopeptidase. This meant that only a tiny fraction (<1/1000) of the native form would remain active producing the peptide GRH(3-44). The whole peptide had a half-life of ~7 minutes when administered intravenously to humans. This enzyme (dipeptidyl peptidase-4) would become a big issue when creating a stable analog.
Differences Between MOD GRF 1-29
MOD GRF 1-29 is a 29 amino acid peptide, with 4 substitutions to make it more stable:
Amino acid 2: Alanine to D-Alanine – Makes the N-terminal bond resistant to degradation by DPP-4.
Amino acid 8: Asparagine to Glutamine – Asparagine is prone to deamination.
Amino acid 15: Glycine to Alanine – Improves helical stability and receptor binding affinity.
Amino acid 27: Methionine to Leucine – Methionine is easily oxidised.
This was used as the basis to develop CJC-1295 by ConjuChem. The tetrasubstituted GRF(1-29) was used as the starting point. CJC-1295 has the additional lysine link and Maleimide group (Drug Affinity Complex/DAC). This allows it to bind to Albumin molecules in the blood stream. Essentially MOD GRF 1-29 is CJC-1295 without the Albumin binding.
For researchers this means that MOD GRF 1-29 is a more stable analog of GRF(1-29). It will still have a short duration of action, whereas the CJC-1295 with DAC has been designed to have a constant duration of action over several days.
Mechanism Of Action
GHRH analogs bind to the GHRH receptor (G-protein coupled receptor) on the Somatotroph cells of the pituitary. This activates the Gs protein and increases cyclic AMP (cAMP) within the cell. This activates the Protein Kinase A pathway to cause:
Release of stored GH granules.
Increase GH gene transcription to stimulate new GH production.
Long term Somatotroph cell proliferation in animal models.
2 Key points to note:
GHRH signalling is inhibited by the hormone Somatostatin, which is produced in the hypothalamus to inhibit GH release. GHRH analogs will increase pulsatile GH release but cannot override the inhibitory effects of Somatostatin. This is one reason why GH will be released in a pulsatile manner in response to GHRH.
GHRH analogs will work synergistically with the Ghrelin receptor agonists (GH Secretagogues: GHRP-2, GHRP-6, ipamorelin). In a study carried out in 1990, Bowers and colleagues demonstrated that sub-maximal doses of a GH releasing peptide combined with GHRH resulted in synergistic increases in GH levels in normal males. This suggests that they work by different mechanisms. This is why GHRH analogs are often tested in combination with secretagogues.
Evidence Available
A lot of evidence you will find online will be from research carried out on similar peptides. There is evidence available for:
CJC-1295 (with DAC). The most common reference to human data is from the long acting version:
Jetté et al., 2005 (Endocrinology). Demonstrated the use of Albumin bioconjugates in rats. Identified CJC-1295 as a long acting GRF analog activating the pituitary GHRH receptor.
Teichman et al., 2006 (Journal of Clinical Endocrinology & Metabolism). Demonstrated that single and multi-dose administration of CJC-1295 increased GH concentrations (2-10x) with an estimated half-life of ~6-8 days. IGF-1 concentrations were increased for 9-11 days following a single dose in healthy adults.
Ionescu & Frohman, 2006 (JCEM). Demonstrated that CJC-1295 administered continuously resulted in maintenance of pulsatile GH secretion. Baseline and total GH outputs were increased.
Sermorelin and GRF(1-29) analogs. Sermorelin has been used clinically for longer and has been used in paediatrics. Tesamorelin is another stabilized GHRH analog that was FDA approved in November 2010 to reduce excess visceral adipose tissue in HIV infected patients suffering from lipodystrophy. This was based on randomized trials (Falutz et al., 2007, New England Journal of Medicine). 412 adults were given either Tesamorelin or Placebo for 26 weeks in a double blind, placebo controlled trial. This shows that the GHRH pathway can be effectively targeted in highly controlled trials.
MOD GRF 1-29. There is very little evidence available for MOD GRF 1-29. Whilst the chemical properties of the tetrasubstituted form are well understood and used as the basis for CJC-1295, there is very little peer reviewed evidence for the pharmacokinetics/effectiveness of MOD GRF 1-29 on its own. Often values you will find online (like half-life) are extrapolated. Be wary of these.
Reasons For Using MOD GRF 1-29
Despite there being little evidence available, MOD GRF 1-29 is still popular in research. Reasons for this are due to the mechanism:
Short acting – No DAC so will cause a short burst of stimulation. Can be used to look at the pituitary response to discrete GHRH signals.
More stable – 4 substitutions to the most documented degradation pathways mean it should be more stable than the natural GRF(1-29).
Easy to combine with secretagogues – As the GHRH pathway interacts with the ghrelin receptor pathway, it is often used with GHRPs to investigate synergistic effects.
Considerations
Like any research peptide, your results will only be as good as your peptide. Small errors in synthesis can affect the behavior of your analog. When purchasing a peptide you would want to ensure that:
They provide a COA for each batch of peptide.
They provide HPLC data and a Chromatogram showing the purity.
They provide Mass Spectrometry to confirm that the molecular weight is correct for the expected sequence.
Clearly state that it is for research use only, with storage information for the lyophilized powder.
Companies like Generic Peptides will provide a COA for each batch of peptide. This should be applied to all compounds within your study.
It can be useful to keep compounds separated. GHRH analogs target the GH pathway. Typically if you are investigating metabolic pathways you will use a different compound. For example, semaglutide research peptide targets the GLP-1 receptor. They act on different receptors so you cannot make conclusions from one to the other.
Regulations & Anti-Doping
MOD GRF 1-29 is not FDA approved. It should only be used for research in the lab.
Growth Hormone Releasing Hormone and its analogs (CJC-1295, Sermorelin, Tesamorelin) are banned in sport by the World Anti-Doping Agency. They are banned in and out of competition (S2.2.4).
Considerations
Some considerations when researching MOD GRF 1-29:
Human Pharmacokinetics – Little controlled data available on half life and GH response to tetrasubstituted peptide.
Long Term Effects – Studies on CJC-1295 suggest that pulsatility is maintained. However we do not know what the long term effects of repeated short acting GHRH stimulation will have on Somatotroph function.
Head to Head Studies – Little head to head studies between MOD GRF 1-29, Sermorelin and CJC-1295.
Overall the most defendable position is that it is a well designed and chemically stabilized analog of GRF(1-29). However much of its reputation comes from evidence around other similar compounds.
FAQ
Is MOD GRF 1-29 the same as CJC-1295?
No. MOD GRF 1-29 is simply the tetrasubstituted GRF(1-29). CJC-1295 (with DAC) is the same sequence but with an Albumin binding component to increase the duration of action from minutes to days. MOD GRF 1-29 is often referred to as CJC-1295 without the DAC.
How different is MOD GRF 1-29 to Sermorelin?
Sermorelin is the native GRF(1-29). MOD GRF 1-29 has had 4 substitutions made to amino acid 2, 8, 15 and 27 to help prevent enzymatic breakdown.
Is there any human trial data for MOD GRF 1-29?
Most human data is from CJC-1295 (with DAC) and Sermorelin. There is limited peer reviewed data for MOD GRF 1-29.
Why is MOD GRF 1-29 often used in combination with GHRPs?
GHRH analogs and Ghrelin receptor agonists target different receptors and have been shown to have synergistic effects on GH. This can be useful when investigating the interaction between the two pathways.
References
Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YC, Felix AM. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. J Clin Invest. 1986;78(4):906-913.
Bowers CY, Reynolds GA, Durham D, Barrera CM, Pezzoli SS, Thorner MO. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. J Clin Endocrinol Metab. 1990;70(4):975-982.
Jetté L, Léger R, Thibaudeau K, et al. 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. Endocrinology. 2005;146(7):3052-3058.
Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805.
Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797.
Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370.
U.S. Food and Drug Administration. Determination that GEREF (sermorelin acetate) was not withdrawn from sale for reasons of safety or effectiveness. Federal Register. 2013;78:14095-14096.
World Anti-Doping Agency. The 2026 Prohibited List. Section S2.2.4. https://www.wada-ama.org/en/prohibited-list
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