Mod GRF 1-29 (CJC-1295 NO DAC) (5mg)

Modified GRF (1-29) Peptide

Modified GRF (1-29), or Mod GRF (1-29), is a synthetic peptide analog of growth hormone-releasing hormone (GHRH). It was first developed in the 1980s when studies indicated that the first 29 amino acids of GHRH may possess all of the biological roles associated with the full-length 44 hormone.^[1] The initially designed peptide, known as GRF (1-29), is the shortest segment of GHRH, and appears to possess all the properties of the full-length hormone. This truncated synthetic form of GHRH is also known as Sermorelin.
Modified GRF (1-29) is another 29 amino-acid peptide that has undergone alteration to include four substituted amino groups in its chain.^[2] These modifications occur at positions 2, 8, 15, and 27, where certain amino acids are substituted with others that may enhance the peptide’s potential. At position 2, the amino acid alanine (Ala) is replaced with D-alanine (D-Ala), which is the mirror image of the natural L-alanine. This change is believed to potentially increase the peptide’s resistance to enzymatic degradation, possibly improving its overall stability. In position 8, asparagine (Asn) is substituted with lysine (Lys), an amino acid characterized by a positively charged side chain. This alteration might enhance the peptide’s binding affinity to the Growth Hormone-Releasing Hormone (GHRH) receptor, potentially increasing its biological activity. At position 15, histidine (His) is replaced with D-phenylalanine (D-Phe), another D-amino acid. It is suggested that this substitution could make the peptide more resistant to enzymatic breakdown, thereby enhancing its stability. Finally, at position 27, cysteine (Cys) is replaced with N-methylglycine, also known as sarcosine (Sar). This modification may potentially increase the peptide’s half-life by protecting it from enzymatic cleavage and degradation.

Overall, the intention behind these amino modifications is to protect the peptide from degradation and improve its half-life. The modification also appears to increase the binding affinity to GHRH receptors. The name Mod GRF (1-29) clarifies that the modified peptide differs from GRF (1-29) as a result of changes in four of its amino acids. Modified GRF (1-29) is structurally identical to CJC-1295 without DAC, as CJC-1295 is normally a Mod GRF (1-29) with the addition of a DAC complex to further improve the pharmacokinetics of the molecule.

Specifications

Molecular Weight: 3367.95 g/mol

Molecular Formula: C₁₅₂H₂₅₂N₄₄O₄₂

Sequence: H-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2

Synonyms: Mod GRF (1-29)

Mod GRF (1-29) Research

Modified GRF (1-29) and Pituitary Gland Cells
Mod GRF (1-29) is hypothesized to function primarily by binding to GHRH receptors on the cells of the anterior pituitary gland, possibly interacting with specific binding sites on these receptor molecules.^[3] The specific pituitary cells that appear to express these receptors and consequently bind GHRH or Mod GRF (1-29) are called somatotroph cells. This binding may cause alterations in the receptor’s shape (conformation), which may initiate a series of molecular events that activate signaling pathways within the pituitary cells. For example, it might promote the activation of G-proteins, which are intracellular signaling proteins believed to be associated with the inner surface of the cell membrane near the GHRH receptor. Activated G-proteins may then stimulate the production of secondary messenger molecules such as cyclic adenosine monophosphate (cAMP) and inositol triphosphate (IP3).^[4] In particular, cAMP might activate protein kinases, enzymes thought to be crucial in phosphorylating or adding phosphate groups to specific target proteins. Once phosphorylated, these transcription factors could enter the cell nucleus and potentially modify the transcription of genes involved in the synthesis and secretion of growth hormone. As a result, the molecular processes potentially initiated by Mod GRF (1-29)’s interaction with the receptor might lead to the fusion of secretory vesicles containing growth hormone with the cell membrane. This fusion could allow the growth hormone to be secreted from the pituitary cells.

A separate study indicated that Mod GRF (1-29) may lead to an increase in total pituitary RNA and growth hormone (GH) messenger RNA (mRNA) levels. This observation could suggest a possible expansion in the population of somatotroph cells, which are responsible for producing growth hormone in the anterior pituitary gland. The researchers posited that the peptide “caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images.”^[5]

Modified GRF (1-29) and Growth Mediators
Although no studies have directly examined the actions of Mod GRF (1-29) in its tetrasubstituted form, some researchers have extensively investigated partially modified versions. Notably, one study suggested that partially modified Mod GRF (1-29) might modulate the GH-IGF-1 axis following its interaction with somatotroph cells.^[6] Specifically, it appeared to induce a significant increase—approximately 70-107%—in the mean 12-hour release of growth hormone by somatotroph cells in the anterior pituitary gland.

In conjunction with the observed rise in growth hormone, it is understood that GH may stimulate the production of insulin-like growth factor 1 (IGF-1), another growth mediator.

IGF-1 is considered the main anabolic mediator of GH and is synthesized primarily in liver cells, but also in various other cell types under the influence of GH. In the study, IGF-1 levels also seemed to increase by approximately 28%, indicating a possible increase in the functionality of the GH-IGF-1 axis. This elevation was associated with an increase in skin tissue thickness, which might be due to the anabolic actions of GH and IGF-1 on collagen-producing skin cells like fibroblasts. Additionally, there was a notable increase in muscle tissue hypertrophy, leading to an average net gain of lean mass of about 2.77 pounds. These findings suggest that Mod GRF (1-29) may potentially induce significant increase in GH and IGF-1, which might promote skin cell proliferation and muscle tissue hypertrophy.

Modified GRF (1-29) and Cardiac Function
Research in rodent models has suggested that Modified GRF (1-29) and other GHRH derivatives may improve the capacity of the heart to pump blood, even following cardiac dysfunction.^[7] More specifically, the researchers comment that “Various studies [suggest] that GHRH agonists promote repair of cardiac tissue, producing improvement of ejection fraction and reduction of infarct size in rats, reduction of infarct scar in swine, and attenuation of cardiac hypertrophy in mice.”

Modified GRF (1-29) and the Intestine
Research in monkeys suggested that the peptide may bind with vasoactive intestinal peptide (VIP) receptors to potentially improve bowel motility. Improved bowel movement is considered to be crucial in inflammatory bowel diseases. The peptide appears to interact with VIPC1, present on the smooth muscle of the reproductive, gastrointestinal, and urinary systems.^[8,9]

Modified GRF (1-29) and Thyroid Hormone
Malfunctioning of the thyroid gland is often associated with concomitant issues in growth hormone release. Research studies have suggested that research models of hyperthyroidism under the influence of thyroid replacement hormone may indicate stronger reactions to GRF, providing a possible link between thyroid hormone and growth hormone.^[10] The scientists commented “These data indicate that thyroid hormone […] enhances the responsiveness of the somatotroph to GRF (1-29).”

Modified GRF (1-29) and Potential Synergism with GHSs
It is believed that when Mod GRF (1-29) is combined with ghrelin mimetics—compounds that imitate the action of the hormone ghrelin—it may produce synergistic actions. Ghrelin mimetics, also known as Growth Hormone Secretagogues (GHSs), are thought to stimulate the release of growth hormone by activating ghrelin receptors rather than the GHRH receptors located in the anterior pituitary gland. Since Mod GRF (1-29) and ghrelin mimetics target different receptors, their concurrent exposure in laboratory and in vitro models might enhance growth hormone release more than either agent alone. Studies have suggested that combining Mod GRF (1-29) with GHS compounds, like Growth Hormone-Releasing Peptide-6 (GHRP-6) and Growth Hormone-Releasing Peptide-2 (GHRP-2), may lead to greater increases in Insulin-Like Growth Factor 1 (IGF-1) levels compared to exposure to each peptide individually.

For instance, one study observed that the combination of GHRP-6 with the unmodified form of Mod GRF (1-29) resulted in an apparent increase in IGF-1 levels by more than 65%.^[11] Another study reported that GHRP-2 alone may lead to a 47-fold increase in pulsatile GH secretion, whereas GHRH-analogs alone could result in a 20-fold increase.^[12] Interestingly, the combination of both GHRH and GHRP-2 has been associated with a 54-fold increase in GH secretion compared to controls. This suggests that the combination might amplify GH release more positively than either compound alone, possibly due to the convergence of different signaling pathways. Furthermore, factors such as insulin-like growth factor 1 (IGF-1) levels may modulate the efficacy of GHRH and GHRP treatments differently. Higher IGF-1 levels seem to enhance the GH secretion induced by GHRH analogs like Mod GRF (1-29).

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