Mod GRF 1-29 (CJC-1295 no DAC)
Mod GRF 1-29, also known as CJC-1295 no DAC, is a synthetic analogue of Growth Hormone Releasing Hormone (GHRH) developed to replicate and enhance the biological activity of the active fragment of the endogenous hormone. This peptide is based on the scientific observation that the first 29 amino acids of GHRH are responsible for the entire biological function of the full 44–amino-acid molecule. From this discovery came GRF 1-29, or Sermorelin, which, however, displayed an extremely short half-life due to its high susceptibility to enzymatic degradation. To overcome this limitation, strategic modifications were introduced into the sequence, replacing certain amino acids with more stable variants resistant to cleavage. The result is Mod GRF 1-29, originally called “tetra-substituted GRF 1-29,” which today represents one of the most widely used analogues in research for studying GH physiology thanks to its prolonged half-life and increased receptor affinity.
When Mod GRF 1-29 binds to GHRH receptors (GHRH-R), it stimulates the somatotrope cells of the pituitary gland to release growth hormone in a pulsatile manner, respecting the body's natural physiology. This release leads to an increase in circulating IGF-1 levels, with indirect effects on metabolism, cellular growth, tissue regeneration, muscle functionality, and bone health. Its superior stability compared to the original GRF 1-29 allows for longer-term studies, offering researchers a more reliable model for analyzing the endocrine mechanisms regulated by the GH/IGF-1 axis.
Development and peptide structure
The development of Mod GRF 1-29 is tied to the need to overcome the extreme metabolic fragility of natural GRF 1-29. Although the peptide retained full biological activity, it was rapidly inactivated by circulating enzymes within minutes. For this reason, substitutions were introduced at key positions of the amino acid chain, improving stability and prolonging its duration of action while preserving effective binding to GHRH receptors. These modifications made Mod GRF 1-29 an especially useful analogue for studying not only acute GH release but also the endocrine and tissue responses emerging from moderate yet longer-lasting stimulation.
Beyond simple stabilization, the introduced modifications allowed for a more selective receptor interaction, maintaining an effective balance between potency, duration, and physiological activity. This balance is the reason why Mod GRF 1-29 is now employed in multiple research contexts, including studies on metabolism, cardiac function, and cellular regeneration.
Gastrointestinal effects and receptor interactions
One of the most fascinating aspects in studying GHRH analogues involves potential interactions with receptors not exclusively related to the GH axis. Some studies in animal models—particularly in primates—have shown that certain analogues structurally similar to Mod GRF 1-29 may interact with VPAC1 receptors, part of the Vasoactive Intestinal Peptide (VIP) receptor family. These receptors are highly expressed in the gastrointestinal tract and regulate functions such as motility and intestinal secretion.
In some research, this interaction resulted in a substantial increase in intestinal motility in primates, causing severe diarrhea during prolonged infusions of particularly potent analogues. In vitro studies have shown that small differences in peptide structure can profoundly alter binding profiles to these alternative receptors, highlighting the importance of assessing the receptor specificity of each GHRH variant.
These findings underscore the complexity of the relationships between chemical structure, receptors involved, and physiological outcomes, and they are essential for ensuring that each analogue is studied in an appropriate context, considering the wide differences among animal species.
Effects on metabolism, pancreas, and diabetes
Several studies have shown that GHRH agonists have potential far beyond GH modulation alone. In experimental models, analogues of the GHRH family have demonstrated the ability to promote proliferation of pancreatic β-cells, improving insulin secretion and contributing to more efficient glucose regulation. These findings place Mod GRF 1-29 in a particularly interesting research area for studying diabetes and conditions requiring functional restoration of pancreatic cells, including pancreatic islet transplantation, where GHRH agonists appear to improve cellular integration and survival.
Cardiac and regenerative effects
GHRH agonists also show significant effects on the cardiovascular system. Animal models have documented improvements in ejection fraction, a reduction in infarct size, and a decrease in cardiac hypertrophy following stimulation with GHRH analogues. These results have led to the discovery of an unexpected role of GHRH in myocardial protection and regeneration, making Mod GRF 1-29 a relevant tool for researching cytoprotective pathways involved in cardiac recovery after ischemic events.
Action on the eye, nervous system, and tissue healing
GHRH receptors have also been identified in extra-endocrine areas such as ocular tissues and the central nervous system. In studies on models of diabetic retinopathy, GHRH agonists have demonstrated neuroprotective effects, reducing neuronal damage and supporting cellular vitality. Other experiments have shown improvements in wound healing processes, thanks to favorable modulation of inflammatory responses. These findings greatly expand the understanding of the role of GHRH receptors beyond the pituitary axis, showing how they may influence the immune system, peripheral regeneration, and neuronal function.
Mod GRF 1-29 and thyroid function
Research on GHRH analogues has also extended to studying the relationship between hypothyroidism and growth hormone secretion. It has been observed that individuals with primary hypothyroidism show a reduced response to GRF stimulation. However, during T4 replacement therapy, the response to GHRH improves significantly, with increases in both GH peak and area under the curve. This demonstrates that thyroid function directly affects the sensitivity of pituitary cells to GHRH stimulation—an essential factor to consider in experimental models using Mod GRF 1-29.
Scientific References
1. PMC2787983
2. PubMed 31070727
3. Studio su ipotiroidismo e GH
Notes and Warnings
Questo prodotto è destinato esclusivamente a uso di ricerca.
Non è destinato all’uso umano, medico, diagnostico o veterinario.
