CJC-1295 DAC Peptide and Hormonal Regulation

CJC-1295 DAC is a peptide hypothesized to mimic the function of growth hormone-releasing hormone (GHRH), potentially enhancing endogenous growth hormone (GH) production. This peptide is a synthetic analog of GHRH, composed of 29 amino acids.⁽¹⁾

Notably, CJC-1295 DAC represents the shortest functional analog of GHRH that appears to retain the potential to stimulate GH release from somatotroph cells in the pituitary gland. Additionally, four of the original amino acids in this sequence are substituted in CJC-1295 DAC, presumably to improve its pharmacokinetics and extend its half-life.

Image 1: Chemical structure of CJC 1295 DAC Peptide

Mechanism of Action

The DAC component is a biochemical complex thought to further prolong the half-life of the peptide. This enhancement is attributed to the DAC’s potential to bind to plasma proteins. Specifically, the DAC component involves attaching a lysine derivative, N-epsilon-3-maleimidopropionamide, to the C-terminus of CJC-1295 DAC. The integration of this modified amino acid sequence with the DAC component may support the pharmacokinetics of CJC-1295 DAC, potentially extending its half-life to approximately 8 days. Concurrently, it maintains a significant affinity for GHRH receptors, similar to the affinity of CJC-1295 without DAC.⁽²⁾

CJC-1295 without DAC also holds relevance in contemporary research. For instance, the combination of CJC-1295 without DAC and Ipamorelin has been studied for its synergistic potential. This blend of GHRH analogs with peptides that seemingly activate ghrelin receptors in the pituitary gland is posited to induce a more substantial GH synthesis response from somatotroph cells.⁽³⁾

CJC-1295 DAC Peptide Half life

CJC-1295 DAC incorporates Drug Affinity Complex (DAC) technology, which contrasts significantly with the naturally occurring growth hormone-releasing hormone (GHRH) that has a half-life of approximately 7 minutes. Studies indicate that CJC-1295 without DAC exhibits an extended half-life of about 30 minutes due to its truncated 29 amino acid structure, with four amino acids substituted to enhance its stability.

Modifications in the peptide structure occur at specific positions, aiming to improve resistance to enzymatic breakdown by dipeptidyl peptidase-4. These modifications are:

Position 2: Substitution of L-alanine with D-alanine to potentially increase resistance against enzymatic degradation.

Position 8: Replacement of asparagine with glutamine to reduce the likelihood of asparagine rearrangement and amide hydrolysis.

Position 15: Substitution of glycine with alanine, theorized to enhance bioactivity.

Position 27: Replacement of methionine with leucine to potentially prevent methionine oxidation.

These alterations aim to enhance the peptide’s resilience and functional efficacy by reducing enzymatic degradation and improving stability under physiological conditions. Furthermore, the incorporation of DAC technology is believed to extend the half-life of the peptide to approximately 6-8 days.⁽⁴⁾

 

Research

CJC-1295 Peptide and Mechanistic Insights

Researchers conducted two pivotal clinical studies in 2006 to investigate the influence of CJC-1295 DAC. In the first study, CJC-1295 DAC or a control compound was utilized in one of four ascending concentrations. The second study involved repeated exposure of CJC-1295 DAC at a single concentration. Results indicated an apparent increase in growth hormone (GH) and insulin-like growth factor-1 (IGF-I) levels following CJC-1295 DAC exposure.⁽⁵⁾ CJC-1295 DAC is hypothesized to elevate IGF-1 levels by stimulating GH production, which may bind to receptors on liver cells and activate intracellular signaling pathways. This binding might activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, leading to the transcription of the IGF-I gene. The produced IGF-I might then be transported to various target tissues, possibly promoting growth and anabolic impact.

CJC-1295 Peptide and GH, IGF-I Levels

Initial exposure to CJC-1295 DAC peptide in experimental models suggested a significant increase in average GH levels, reportedly by 2- to 10-fold for up to 6 days. Moreover, IGF-I levels appeared to rise by 1.5- to 3-fold for approximately 9-11 days, with elevated levels potentially lasting at least two weeks. Repeated exposure to CJC-1295 DAC seemed to maintain elevated IGF-I levels above baseline for up to 28 days, indicating a cumulative effect.

In a separate 2006 study,⁽⁶⁾ researchers assessed GH pulsatility following a single iteration of CJC-1295 DAC. The results suggested a 50% increase in mean GH secretion and IGF-I levels. It is postulated that CJC-1295 DAC may interact with binding sites on the GHRH receptor protein, initiating molecular processes that activate intracellular signaling proteins such as G-proteins.⁽⁷⁾ These proteins may promote the production of secondary messengers like cyclic adenosine monophosphate (cAMP), which are considered crucial in cellular signaling pathways. The activation of protein kinases by these messengers might lead to the phosphorylation of transcription regulators, influencing gene expression involved in GH production.

CJC-1295 Peptide and Animal-Based Research

Further animal studies⁽⁸⁾ evaluated the potential of CJC-1295 DAC in murine models. In one study, daily exposure of CJC-1295 DAC peptide appeared to normalize growth completely. Administering the peptide every 2 or 3 days appeared to have produced intermediate influence, suggesting interval-dependent action. The study indicated that CJC-1295 DAC might impact mass composition by increasing muscle tissue hypertrophy while potentially reducing fat tissue levels. In GHRHKO murine models, CJC-1295 DAC exposure seemed to preserve normal lean mass levels and maintain subcutaneous fat mass consistent with control levels, unlike in models without exposure, which reportedly exhibited increased fat levels. Additionally, based on the immunohistochemistry images, the researchers state that “CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred.”

CJC-1295 Peptide and Infertility

Research dating back to the early 1990s suggests that CJC-1295 and other growth hormone-releasing factor (GRF) analogs may promote ovulation in infertile female organsims, as these models reportedly showed “a significant increase of both follicular fluid IGF-I levels (compared to the previous cycle) and plasma GH levels immediately.”⁽⁹⁾ Ovulation is considered to be dependent on insulin-like growth factor-1 (IGF-1) and likely influenced by growth hormone (GH) release and cycling. Studies in animal models of superovulation have indicated that both GH and IGF-1 levels may significantly increase around the time of ovulation. These findings indicate that the exogenous exposure of GH secretagogues, such as CJC-1295, might induce appropriate ovulation.

 
NOTE: These products are intended for laboratory research use only. This peptide is not intended for personal use. Please review and adhere to our Terms and Conditions before ordering.

 

References:

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4. Van Hout MC, Hearne E. Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions. Subst Use Misuse. 2016 Jan 2;51(1):73-84. doi: 10.3109/10826084.2015.1082595. Epub 2016 Jan 15. PMID: 26771670. https://pubmed.ncbi.nlm.nih.gov/26771670/
5. 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 Mar;91(3):799-805. doi: 10.1210/jc.2005-1536. Epub 2005 Dec 13. PMID: 16352683. https://pubmed.ncbi.nlm.nih.gov/16352683/
6. 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 Dec;91(12):4792-7. doi: 10.1210/jc.2006-1702. Epub 2006 Oct 3. PMID: 17018654. https://pubmed.ncbi.nlm.nih.gov/17018654/
7. Martin, B., Lopez de Maturana, R., Brenneman, R., Walent, T., Mattson, M. P., & Maudsley, S. (2005). Class II G protein-coupled receptors and their ligands in neuronal function and protection. Neuromolecular medicine, 7(1-2), 3–36. https://link.springer.com/article/10.1385/NMM:7:1-2:003
8. Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1290-4. doi: 10.1152/ajpendo.00201.2006. Epub 2006 Jul 5. PMID: 16822960. https://pubmed.ncbi.nlm.nih.gov/16822960/
9. Volpe A, Coukos G, Barreca A, Giordano G, Artini PG, Genazzani AR. Clinical use of growth hormone-releasing factor for induction of superovulation. Hum Reprod. 1991 Oct;6(9):1228-32. doi: 10.1093/oxfordjournals.humrep.a137517. PMID: 1752922. https://pubmed.ncbi.nlm.nih.gov/1752922/
10. Image source: Lucie Jetté, Roger Léger, Karen Thibaudeau, Corinne Benquet, Martin Robitaille, Isabelle Pellerin, Véronique Paradis, Pieter van Wyk, Khan Pham, Dominique P. Bridon, 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, Volume 146, Issue 7, 1 July 2005, Pages 3052–3058, https://doi.org/10.1210/en.2004-1286