Studies suggest two peptides, CJC-1295 and GHRP-6, may interact with somatotrophs, cells in the pituitary gland and hypothalamus. Growth hormone production and control are both considered to include these cells. CJC-1295, a putative analog of GHRH, and GHRP-6 (Growth Hormone Releasing Peptide 2), a putative mimetic of ghrelin receptors, make up the bulk of the mixture.
Studies suggest a synergistic impact between CJC-1295 and GHRP-6 on cells responsible for producing growth hormones is possible. By combining these peptides, somatotroph cells may increase the intensity and frequency of their growth hormone pulses. CJC-1295 seems to target the GHRH receptor pathway, while GHRP-6 may operate on the ghrelin receptor route; this synergistic effect is thought to be achieved by these two compounds’ complementary modes of action.
CJC-1295 and GHRP-6 Peptide Blend Affinity
To all appearances, CJC-1295, or tetra-substituted GRF (1-29), is a synthetic peptide analog of the native GHRH hormone. The first 29 amino acids of GHRH comprise the shortest amino-acid chain that may have an affinity to the GHRH receptors. To prevent fast cleavage by dipeptidyl peptidase-4 and other peptides that tend to result in peptide inactivation, 4 of the original 29 amino acids in CJC-1295 have been changed. Specifically, the 2nd, 8th, 15th, and 27th amino acids seem altered or substituted. In addition, plasma proteins may be bound to CJC-1295 since it now has a drug affinity complex (DAC). CJC-1295 has a lysine derivative termed N-epsilon-3-maleimidopropionamide attached to its C terminus, which is what the DAC component refers to. CJC-1295’s apparent affinity to the GHRH receptors has been preserved, while adding a DAC component can potentially improve the compound’s pharmacokinetics. Experts have praised the peptide since it “was found to be present in plasma beyond 72 h.”
Instead, research suggests GHRP-6 is a hexapeptide with structural similarities with other synthetic growth hormone-releasing peptides. It may exert its impact via binding to the ghrelin receptor expressed on the surface of pituitary cells and certain hypothalamus neurons. GHRP-6 binds to the growth hormone secretagogue receptor (GHS-R1a), which then seems to activate. Since ghrelin seems to be their primary natural ligand, these receptors are also known as ghrelin receptors. Data suggests that GHRP-6 may bind to these receptors and stimulate a calcium response and protein kinase C activity inside cells. Growth hormone secretion from pituitary cells seems to be stimulated by GHRP-6, and the CD36 receptors may be a target for GHRP-6. Potential functions of CD36 receptors include modifying immunological responses by controlling phagocytosis and inflammation and serving as a scavenger receptor for lipids to facilitate their absorption. CD36 pathways may contribute to the control of angiogenesis as well.
CJC-1295 and GHRP-6 Peptide Blend: Somatotroph Cells
Studies suggest that somatotroph cells may be a target of CJC-1295 because of the GHRH receptor they express. In particular, CJC-1295 may initiate a cascade of molecular processes by binding to locations on the receptor protein that cause conformational changes in the receptor structure. Proteins in intracellular signaling may serve as molecular switches that set off these processes. After being activated, these so-called G-proteins may promote the creation of second messengers, such as cyclic adenosine monophosphate (cAMP) and inositol trisphosphate (IP3). Protein kinases are thought to alter particular proteins and may be activated by second messengers like cAMP. These kinases may phosphorylate transcription factors, which are proteins that regulate gene expression and exert control over biological activities. To possibly affect genes involved in growth hormone production, phosphorylated transcription factors may reach the nucleus of somatotroph cells.CJC-1295 binding seems to initiate a cascade of events that results in somatotroph cells releasing growth hormone from vesicles. Scientists speculate that the peptide may stimulate somatotrophs to produce more growth hormone, leading to “an overall increase in GH secretion… by 46%.” In turn, insulin-like growth factor-1 (IGF-1) seems to be a significant anabolic mediator of growth hormone’s effects. The levels of IGF-1 also rose, presumably by 45%. As suggested by studies, CJC-1295 may increase “GH concentrations by 2- to 10-fold.”
Since CJC-1295 and GHRP-6 seem to interact with receptors in the central nervous system, especially in the pituitary gland cells known as somatotrophs, this combination may have synergistic potential. Hypothesized to have neuroendocrine functions, these peptides prompt somatotrophs to secrete growth hormones. In the pituitary gland, CJC-1295 seems to bind the GHRH receptors, which may trigger conformational changes and the activation of intracellular signaling cascades that result in increased growth hormone synthesis. However, GHRP-6 may preferentially bind to GHS-R1a receptors (also called ghrelin receptors) and activate an intracellular calcium response and protein kinase C activity rather than generate cAMP. This may also set off a chain reaction of molecular processes that ultimately lead to the discharge of growth hormones.
CJC-1295 & GHRP-6 blend for sale is available at Core Peptides if you are a researcher interested in further studying the compounds mentioned in this article.
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[ii] Jetté, L., Léger, R., Thibaudeau, K., Benquet, C., Robitaille, M., Pellerin, I., Paradis, V., van Wyk, P., Pham, K., & Bridon, D. P. (2005). 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, 146(7), 3052–3058. https://doi.org/10.1210/en.2004-1286
[iii] Sun, Q., Ma, Y., Zhang, L., Zhao, Y. F., Zang, W. J., & Chen, C. (2010). Effects of GH secretagogues on contractility and Ca2+ homeostasis of isolated adult rat ventricular myocytes. Endocrinology, 151(9), 4446–4454. https://doi.org/10.1210/en.2009-1432
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