CJC-1295 and GHRP-6 Blend – Potential Actions on Growth Hormone Synthesis & Anabolic Signaling

CJC-1295 and GHRP-6 are synthetic research peptides that are of interest to researchers primarily for their potential to interact with pituitary gland cells. They may interact with receptors on the pituitary gland that are involved in the synthesis of growth hormone (hGH) – a protein-based hormone with significant anabolic & fat-burning potential. Thus, CJC-1295 and GHRP-6 may be studied in combination, as they appear to play a role in stimulating growth hormone (hGH) synthesis by pituitary gland cells via separate receptors.

CJC-1295 appears to interact with the main receptors on the anterior pituitary gland cells, which normally respond to GHRH (growth hormone-releasing hormone). On the other hand, GHRP-6 may interact with an alternative set of receptors that normally respond to a particular hunger hormone called ghrelin. Researchers are actively investigating the potential complementary or synergistic actions of the two peptides, as they appear to interact via different mechanisms and thus may exert an even greater stimulus on hGH-producing pituitary gland cells.

 

Research

Peptide Structures of CJC-1295 and GHRP-6

CJC-1295 and GHRP-6 have distinct structures. Interaction with catalyzing forces found in research models has the potential to result in different receptor affinities. CJC-1295 is a synthetic peptide based on the first 29 amino acids of the endogenous growth hormone-releasing hormone (GHRH). However, this 29-amino acid structure was modified to replace four specific amino acids — at positions 2, 8, 15, and 27 — that potentially make it less vulnerable to rapid clipping and deactivation by enzymes such as dipeptidyl peptidase-4.

By slowing this enzymatic breakdown, the peptide might remain intact long enough to continue signaling. In addition to these swaps, CJC-1295 is thought to include a drug-affinity complex (DAC) tag at its carboxyl end. Chemically described as an N-Ε-3-Maleimidopropionamide derivative, this tag may bind to abundant plasma proteins, thereby mitigating its rapid clearance by detoxification mechanisms. Early pharmacokinetic studies, such as those by Jetté et al., comment that the peptide “was found to be present in plasma beyond 72 h,” which is considerably longer than the 10-minute half-life of the unmodified GHRH 1-29 sequence.⁽¹⁾ That said, GHRP-6 peptide was pioneered by researchers such as Bowers et al., and its structure was not based on an endogenously occurring hormone, but rather an analog of a neuromediator called met-enkephalin.⁽²⁾

GHRP-6 is a synthetic hexapeptide.

Despite this structural basis, the GHRP-6 peptide does not have any related opioid receptor signaling. Instead, GHRP-6 appears to interact with the receptors of another hormone called ghrelin. This is a hunger hormone that may interact with pituitary gland cells via a different set of receptors, called ghrelin receptors or Growth Hormone Secretagogue Receptors (GHS-receptors).

CJC-1295 and GHRP-6 Receptor Affinities

Research by Culhane et al. suggests that peptides like CJC-1295 may bind to the GHRH receptor on anterior pituitary gland cells, triggering a chain reaction.⁽³⁾ The receptor may activate intracellular G proteins, which then boost levels of a small molecule called cAMP. Rising cAMP is believed to potentially contribute to the “turning on” of protein kinase A, an enzyme that helps switch on the cell’s machinery for making and releasing hGH. More specifically, this may promote intracellular events such as calcium influx and transcriptional changes, which are needed to drive hGH synthesis and release.

In comparison to endogenous GHRH, the GHRH receptor might stay engaged and keep the cAMP pathway active over an extended period. In turn, pituitary cells may be nudged into producing more hGH or keeping hGH production going for longer than usual. In contrast, GHRP-6 appears to target pituitary gland cells by binding to their GHS-receptors, also called GHS-R1a. Similar to their activation by ghrelin, research by Yin et al. highlights that peptides like GHRP-6 may activate an enzyme called phospholipase C (PLC) when docking to the receptor.⁽⁴⁾ PLC then may cleave a membrane lipid (PIP₂) into two “second messengers”: IP₃ (inositol 1,4,5-trisphosphate) and DAG (diacylglycerol). IP₃ may diffuse into the cell’s interior and open calcium channels on the endoplasmic reticulum, causing stored calcium to flood into the cytoplasm.

Meanwhile, DAG remains in the membrane and helps activate protein kinase C (PKC). The combined surge in intracellular calcium and PKC activity serves as the key signal that drives growth hormone–loaded granules toward the cell surface, where they fuse with the membrane and release hGH. Because this IP₃/DAG-driven pathway is distinct from the cAMP-focused mechanism of GHRH analogues like CJC-1295, researchers are studying whether using both peptides together may yield a stronger or more sustained boost in hGH production.

Interestingly, GHRP-6 may also have affinity to receptors unrelated to the pituitary gland cells, such as the CD36 receptors. CD36 is a scavenger receptor found on macrophages and endothelial cells. Research by Demers et al. suggests that the peptide’s contact points may be a stretch of CD36 between amino acids 132 and 177, with a critical interaction at methionine-169.⁽⁵⁾ The scientists also suggested that GHRP-6 may displace oxidized low-density lipoprotein (oxLDL) from this same region, suggesting that it docks into the CD36 pocket that normally recognizes modified lipoproteins.

By binding CD36 at or near Met169, GHRP-6 may partially block oxLDL uptake by macrophages and interfere with thrombospondin-1 signaling in the endothelium. In experimental models, this may translate into reduced foam cell formation and altered angiogenic responses—mechanisms that might contribute to the anti-atherosclerotic actions of GHRPs.

Individual and Synergistic Potential of the CJC-1295 and GHRP-6 Blend

Both CJC-1295 and CHRP-6 have been studied separately regarding their potential hGH-stimulating actions on anterior pituitary gland cells. Notably, experimental work by Teichman and colleagues indicates that CJC-1295 may boost “GH concentrations by 2- to 10-fold for 6 d or more”.⁽⁶⁾ Moreover, the researchers reported that while the peak was sustained for almost a week, it appeared to occur about two hours after exposure.

Further research by Micle et al. suggests that GHRP-6 may also provoke a substantial rise in hGH levels on its own.⁽⁷⁾ The researchers observed that a single exposure may lift peak GH concentrations to around 60 mU/L—approximately a 30- to 50-fold jump over baseline (which typically sits near 1–2 mU/L), and over 3-fold compared to physiological peaks (up to 20 mU/L).

Moreover, Micle et al. investigated the combined potential of GHRP-6 with a GHRH-analog (although not CJC-1295, but the full GHRH sequence), and they suggested that the blend may push peak GH into the neighborhood of 140 mU/L, roughly doubling the GHRP-6–only response and representing a ~70- to 100-fold increase over baseline.⁽⁷⁾ These observations suggest that combining a ghrelin-mimetic peptide like GHRP-6 with a GHRH-based compound like CJC-1295 may potentially amplify hGH release more than either agent alone, perhaps by engaging both the GHS-R and GHRH-R pathways to deliver a more sustained or synergistic stimulus to somatotroph cells in research settings.

Cordido et al. also evaluated the synergistic potential of GHRP-6 with GHRH-analogs (again, not CJC-1295, but the full GHRH sequence).⁽⁸⁾ When pituitary cells were exposed to GHRP-6 alone, the average GH peak rise was suggested to be about 6 mU/L (15.7 ± 4.4 pg/L), compared with a baseline near zero. In contrast, exposure to a GHRH analogue alone appeared to yield a smaller GH peak of roughly 2.6 mU/L (6.8 ± 1.1 pg/L), implying that GHRP-6 may induce about a 2.3-fold larger acute response than GHRH in this setting.

Looking at overall secretion, the GH area under the curve (AUC) with GHRP-6 alone was suggested to be around 260 mU·min/L (674 ± 187 pg·min/L), versus 159 mU·min/L (412 ± 71 pg·min/L) for GHRH, again suggesting a roughly 1.6-fold greater cumulative release with GHRP-6. Most notably, when pituitary cells are simultaneously challenged with both GHRP-6- and GHRH-type peptides, mean GH peaks appeared to climb to 16.3 mU/L (42.2 ± 10.9 pg/L)—approximately 2.7 times the GHRP-6–only peak and 6.2 times the GHRH-only peak.

The combined AUC also jumps to about 729 mU·min/L (1,894 ± 784 pg·min/L), nearly 2.8-fold higher than GHRP-6 alone and 4.6-fold higher than GHRH alone.⁽⁸⁾ It’s important to note, however, that the experiments used related GHRH analogues rather than CJC-1295, so the precise degree of synergy between the latter and GHRP-6 remains to be established.

Anabolic Potential of the CJC-1295 and GHRP-6 Blend

The apparent increase in hGH levels by CJC-1295 and GHRP-6 may also upregulate anabolic signaling. Specifically, growth hormone may engage receptors on hepatocytes, myocytes, and other target cells. This may play a role in triggering intracellular cascades such as the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway.

Research by Himpe et al. suggests that upon receptor binding, associated JAK kinases might phosphorylate STAT proteins, which may then translocate into the nucleus and bind to specific response elements on DNA.⁽⁹⁾ This sequence of events may drive the transcription of genes responsible for insulin-like growth factor-1 (IGF-1) production, the principal anabolic effector of GH.

As suggested by the experiments mentioned above, both CJC-1295 and GHRP-6 are expected to boost GH release and, consequently, IGF-1 synthesis. Indeed, Teichman et al. suggest that CJC-1295 may increase average IGF-1 concentrations by approximately 1.5- to 3-fold throughout 9 to 11 days, and that continued exposure to the peptide may help maintain these elevated levels for up to 28 days.⁽⁶⁾ Unfortunately, no studies have measured IGF-1 level changes when investigating the potential of GHRP-6 alone or in combination with GHRH-analog only.

Considering the synergistic potential suggested by the experiments of Micic et al. and Cordido et al., a similar synergistic increase in the anabolic signalling by IGF-1 levels may be expected.⁽⁷⁾⁽⁸⁾ Future research should aim at investigating this specific synergistic potential between CJC-1295 and GHRP-6 in laboratory settings.

You can find CJC-1295 & GHRP-6 Blend for sale with 99% purity, on our website (available for research use only).

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:

1. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. 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 Jul;146(7):3052-8. doi: 10.1210/en.2004-1286. Epub 2005 Apr 7. PMID: 15817669.
2. Bowers CY. History to the discovery of ghrelin. Methods Enzymol. 2012;514:3-32. doi: 10.1016/B978-0-12-381272-8.00001-5. PMID: 22975043.
3. Culhane KJ, Liu Y, Cai Y, Yan EC. Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors. Front Pharmacol. 2015 Nov 5;6:264. doi: 10.3389/fphar.2015.00264. PMID: 26594176; PMCID: PMC4633518.
4. Yin Y, Li Y, Zhang W. The growth hormone secretagogue receptor: its intracellular signaling and regulation. Int J Mol Sci. 2014 Mar 19;15(3):4837-55. doi: 10.3390/ijms15034837. PMID: 24651458; PMCID: PMC3975427.
5. Demers A, McNicoll N, Febbraio M, Servant M, Marleau S, Silverstein R, Ong H. Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study. Biochem J. 2004 Sep 1;382(Pt 2):417-24. doi: 10.1042/BJ20040036. PMID: 15176951; PMCID: PMC1133797.
6. 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.
7. Micic D, Popovic V, Kendereski A, Macut D, Casanueva FF, Dieguez C. Growth hormone secretion after the administration of GHRP-6 or GHRH combined with GHRP-6 does not decline in late adulthood. Clin Endocrinol (Oxf). 1995 Feb;42(2):191-4. doi: 10.1111/j.1365-2265.1995.tb01861.x. PMID: 7734029.
8. Cordido F, Peñalva A, Dieguez C, Casanueva FF. Massive growth hormone (GH) discharge in obese subjects after the combined administration of GH-releasing hormone and GHRP-6: evidence for a marked somatotroph secretory capability in obesity. J Clin Endocrinol Metab. 1993 Apr;76(4):819-23. doi: 10.1210/jcem.76.4.8473389. PMID: 8473389.
9. Himpe E, Kooijman R. Insulin-like growth factor-I receptor signal transduction and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Biofactors. 2009 Jan-Feb;35(1):76-81. doi: 10.1002/biof.20. PMID: 19319849.