Potential Synergistic Actions with Mod GRF (1-29) & GHRP-6 Blend

Modified Growth Hormone Releasing Factor (Mod GRF (1-29)) and Growth Hormone Releasing Peptide-6 (GHRP-6) are research peptides that may interact with different receptors on pituitary cells and possibly trigger the production of growth hormone (hGH).

It is thought that Mod GRF (1-29) is derived from the endogenous Growth Hormone Releasing Hormone (GHRH) and contains its first 29 amino acids. In this peptide, there appear to be changes at positions 2, 8, 15, and 27.⁽¹⁾

• At position 2, alanine is replaced with D-alanine; at position 15, histidine is replaced with D-phenylalanine; and at position 27, cysteine may be replaced with N-methylglycine (also called sarcosine). These might help the peptide resist being broken down by enzymes and extend its half-life.
• At position 8, asparagine may be replaced with lysine, a positively charged amino acid, which might support the peptide’s ability to bind to GHRH receptors.

Mod GRF (1-29) peptide is thought to keep and perhaps even boast a better-supported ability to bind to GHRH receptors on pituitary cells and consequently stimulate hGH production. GHRP-6 is a synthetic hexapeptide that is structurally similar to met-enkephalins. It is believed not to work with opioid receptors. Instead, GHRP-6 is a growth hormone secretagogue (GHS) thought to help release hGH by activating ghrelin receptors on pituitary cells.

These receptors are the main receptors that respond to the hunger signals by ghrelin but also regulate hGH synthesis and bear the name  Growth Hormone Secretagogue Receptor type 1a (GHS-R1a). They appear to be responsible for the hGH-releasing impacts of GHRP-6.⁽²⁾ Because GHRP-6 and Mod GRF (1-29) seem to act on different receptors, they might work together to support hGH production in pituitary cells. There is also some data that GHRP-6 might interact with other receptors, such as CD36, on certain immune cells.⁽³⁾

 

Research

Mod GRF (1-29) and GHRP-6 Blend Interactions with Pituitary Receptors

Research by Sinha et al.. indicates that Mod GRF (1-29) may interact with GHRH receptors on anterior pituitary cells and might trigger a series of intracellular signals that might support hGH synthesis.⁽³⁾ One proposed pathway that Mod GRF (1-29) may activate involves the enzyme adenylyl cyclase. This enzyme is believed to convert adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP).

The rise in cAMP levels is thought to possibly activate protein kinase A (PKA), an enzyme that may add phosphate groups to various cellular proteins. PKA-mediated phosphorylation may modify proteins such as voltage-dependent calcium channels on the cell membrane, which might then open and stimulate secretory vesicles in pituitary cells to release growth hormones. Laboratory experiments by Khorram et al. with Mod GRF (1-29) suggest that the peptide may support growth hormone release by pituitary cells, with one study reporting a 70% to 107% increase in the 12-hour area under the curve of hGH concentrations.

As a result, the increased growth hormone synthesis may also lead to higher production of the insulin-like growth factor 1, with mean levels apparently rising by about 28%.⁽⁴⁾ A separate study by Alba et al. suggests that Mod GRF (1-29) may increase the total amount of pituitary RNA as well as the levels of hGH messenger RNA (mRNA).⁽⁵⁾ This observation might indicate a potential increase in the number of somatotroph cells, which are considered responsible for producing hGH in the first place. Specifically, 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.”

When it comes to GHRP-6, research by Frieboes et al. suggests that it may bind to GHS-R1a receptors on pituitary cells and potentially induce a conformational change in these receptors and induce a nearly threefold increase in growth hormone release compared to control⁽⁶⁾ This change may activate the phospholipase C (PLC) pathway, which in turn may lead to the production of secondary messengers like inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 might facilitate the release of calcium ions from intracellular stores such as the endoplasmic reticulum. This release of calcium may potentially trigger the secretion of hGH from the somatotroph cells in the anterior pituitary gland.

Mod GRF (1-29) and GHRP-6 Blend Synergistic Actions on hGH Synthesis

Sinha et al. suggest that a combination of a GHS like GHRP-6 and a GHRH-agonist such as Mod GRF (1-29) might support growth hormone release more than either agent alone.⁽³⁾ Their research indicates that a GHS alone may lead to a 47-fold increase in pulsatile hGH secretion, while GHRH analogs alone might result in a 20-fold increase.

Interestingly, the combination of both GHRH and GHS appears to be associated with a 54-fold increase in hGH secretion compared to controls. This finding suggests that the combination might potentially amplify hGH release more than either compound by itself, possibly due to the convergence of different signaling pathways. However, it should be noted that the researchers have not specifically tested the Mod GRF (1-29) and GHRP-6 blend, but rather their analogs. The exact rate of synergy expected between these laboratory compounds remains uncertain and requires further research.

Mod GRF (1-29) and GHRP-6 Blend Interactions with Other Receptors

In addition to the GHS-R1a receptor, some researchers like Sabatino et al.. propose that GHRP-6 might also bind to other receptors, such as CD36.⁽⁷⁾ CD36 receptors are found on certain immune cells, and GHRP-6’s interaction with them may impact lipid metabolism, angiogenesis, and immune regulation. For example, activation of the CD36 receptor might be involved in the uptake of oxidized low-density lipoprotein (ox-LDL) by macrophages. Macrophages, which are immune cells that scientists are familiar with for their ability to engulf pathogens and cell debris, may potentially internalize oxLDL particles via CD36. This process might lead to lipid buildup within macrophages, possibly transforming them into foam cells that are thought to play a role in atherosclerosis models.

Some researchers believe that CD36 may also impact angiogenesis, perhaps through its interaction with thrombospondin-1 in endothelial cells. In studies involving competition binding assays, researchers such as Demers et al. have suggested that GHRP-6 and oxLDL might share a common binding site on CD36.⁽⁸⁾ GHRP-6 may compete with oxLDL for attachment to CD36, and reducing oxLDL internalization might help lessen foam cell formation. Additionally, Berlanga et al. have ”suggested that GHRP-6 prevented myocardial injury via a decrease in reactive oxygen species and by the preservation of antioxidant defense systems”^(9). Thus, GHRP-6 may reduce free radical-mediated damage in cardiac cells based on data collected from research models. Whether the addition of Mod GRF (1-29) to GHRP-6 may further support its protective potential in atherosclerosis models remains unclear.

Mod GRF (1-29) and GHRP-6 Blend Interactions with Adipose Cells

Research examining Mod GRF (1-29) and GHRP-6 blend suggests that both peptides might impact the distribution of adipose tissue through their impacts on growth hormone secretion. Growth hormone is thought to have lipolytic actions, especially in visceral fat areas. Kopchick et al. noted that “GH impacts adipose tissue in a depot-specific manner and influences other features of adipose tissue (for example, senescence, adipocyte subpopulations, and fibrosis), all of which [might] influence lipolysis.”⁽¹⁰⁾ This preference may be due to a higher density of growth hormone receptors in visceral adipocytes compared to those in subcutaneous fat cell mass.

Furthermore, research by Dehkhoda et al. suggests that when growth hormone binds to these receptors, it might activate enzymes such as hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), which help break down stored triglycerides into free fatty acids and glycerol.⁽¹¹⁾ In addition, by engaging signaling pathways like JAK/STAT, the growth hormone may trigger the transcription of genes that are involved in lipid mobilization. This process might further promote lipolysis and may potentially reduce visceral fat cell mass. Thus, by stimulating growth hormone release, Mod GRF (1-29) and GHRP-6 blend may indirectly encourage a metabolic shift that favors the reduction of visceral fat cell mass. It’s important to note that under experimental conditions, as central fat depots are metabolized, there might be a relative shift of adipose tissue from visceral to subcutaneous regions rather than a reduction in total fat cell mass.

You can find Mod GRF 1-29 & 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:

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2. Lei T, Buchfelder M, Fahlbusch R, Adams EF. Growth hormone-releasing peptide (GHRP-6) stimulates phosphatidylinositol (PI) turnover in human pituitary somatotroph cells. J Mol Endocrinol. 1995 Feb;14(1):135-8. doi: 10.1677/jme.0.0140135. PMID: 7772238.
3. Sinha, D. K., Balasubramanian, A., Tatem, A. J., Rivera-Mirabal, J., Yu, J., Kovac, J., Pastuszak, A. W., & Lipshultz, L. I. (2020). Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Translational andrology and urology, 9(Suppl 2), S149–S159. doi: 10.21037/tau.2019.11.30
4. Khorram, O., Laughlin, G. A., & Yen, S. S. (1997). Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. The Journal of clinical endocrinology and metabolism, 82(5), 1472–1479. doi: 10.1210/jcem.82.5.3943
5. 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.
6. Frieboes RM, Murck H, Maier P, Schier T, Holsboer F, Steiger A. Growth hormone-releasing peptide-6 stimulates sleep, growth hormone, ACTH, and cortisol release in a normal man. Neuroendocrinology. 1995 May;61(5):584-9. doi: 10.1159/000126883. PMID: 7617137.
7. Sabatino, D., Proulx, C., Pohankova, P., Ong, H., & Lubell, W. D. (2011). Structure-activity relationships of GHRP-6 azapeptide ligands of the CD36 scavenger receptor by solid-phase submonomer azapeptide synthesis. Journal of the American Chemical Society, 133(32), 12493–12506. doi: 10.1021/ja203007u
8. Demers, A., McNicoll, N., Febbraio, M., Servant, M., Marleau, S., Silverstein, R., & Ong, H. (2004). Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study. The Biochemical journal, 382(Pt 2), 417–424. doi: 10.1042/BJ20040036
9. Berlanga, J., Cibrian, D., Guevara, L., Dominguez, H., Alba, J. S., Seralena, A., Guillén, G., López-Mola, E., López-Saura, P., Rodriguez, A., Perez, B., Garcia, D., & Vispo, N. S. (2007). Growth-hormone-releasing peptide 6 (GHRP6) mitigates oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction. Clinical Science (London, England: 1979), 112(4), 241–250. doi: 10.1042/CS20060103
10. Kopchick, J. J., Berryman, D. E., Puri, V., Lee, K. Y., & Jorgensen, J. O. L. (2020). The effects of growth hormone on adipose tissue: old observations, new mechanisms. Nature reviews. Endocrinology, 16(3), 135–146. doi: 10.1038/s41574-019-0280-9
11. Dehkhoda F, Lee CMM, Medina J, Brooks AJ. The Growth Hormone Receptor: Mechanism of Receptor Activation, Cell Signaling, and Physiological Aspects. Front Endocrinol (Lausanne). 2018 Feb 13;9:35. doi: 10.3389/fendo.2018.00035. PMID: 29487568; PMCID: PMC5816795.