Tesamorelin, Modified GRF, and Ipamorelin Peptide Blend Research
The peptide blend of Tesamorelin, Modified gonadotropin-releasing factor (GRF), and Ipamorelin has been suggested to stimulate growth hormone (HGH) synthesis in the pituitary gland.
Tesamorelin is a synthetic peptide believed to mimic the effects of the natural growth hormone-releasing hormone (GHRH). Data suggests that it may trigger growth hormone production from pituitary cells by interacting with GHRH receptors in the pituitary and brain.
Synthetic peptide analog of natural growth hormone-releasing hormone (GHRH) is abbreviated as Mod GRF (Modified Growth Hormone-Releasing Factor) or CJC-1295 sans DAC (Drug Affinity Complex). The shortest GHRH sequence, GRF (1-29), has been tetrasubstituted and seems to activate the GHRH receptors. This suggests that it may trigger the release of growth hormone (GH) via binding to GHRH receptors on pituitary cells.
Studies suggest that the synthetic peptide Ipamorelin may also interact with pituitary cells, but it seems to do so through activating the growth hormone secretagogue (GHS) receptor. The hypothalamus and pituitary gland are to be the brain regions suggested to house these receptors, also known as ghrelin receptors. Research suggests that Ipamorelin may stimulate pituitary cells to produce growth hormone (HGH) by binding to and activating specific receptors on these cells.
The Interaction Between Tesamorelin, Mod GRF, and Ipamorelin Peptides
It has been hypothesized that Tesamorelin, Mod GRF, and Ipamorelin may exert their impact predominantly via the GHRH receptors in the brain and spinal cord and, more specifically, in the anterior pituitary gland, where somatotroph cells are located. Researchers speculate that Tesamorelin and Mod GRF may be two primary activators of these receptors. Tesamorelin’s 44-amino-acid chain has the same amino-acid sequence as GHRH, suggesting an affinity for the GHRH receptors. An acetyl group (CH3CO-) is added to the N-terminus of Tesamorelin, which may improve the peptide’s stability and bioactivity. In addition, a trans-3-hexenoic acid group has been added to the C-terminus of Tesamorelin. This change, called an omega-amino acid modification, may make the peptide more stable against proteolytic enzymes.
Affinity, on the other hand, may be found between Mod GRF and the shortest functional component of GHRH – GHF (1-29), with which it has a lot of structural similarities. Nonetheless, it is altered at four positions: 2, 8, 15, and 27. D-Alanine (D-Ala) is a modified form of the amino acid alanine (Ala) that takes over at position two. The peptide’s stability and resistance to enzymatic degradation might both be enhanced by this alteration. Lysine (Lys) is a modified form of the amino acid asparagine (Asn), which takes its place at position eight. This change may improve the binding affinity of the peptide to the GHRH receptor. Histidine (His) has been switched out for D-Phenylalanine (D-Phe) at position fifteen. Due to this alteration, the peptide’s stability and resistance to enzymatic degradation may improve. N-methyl glycine (Sar) is substituted for the amino acid cysteine (Cys) at position twenty-seven. This change might prolong the peptide’s potential by making it more digestion-resistant.
Research suggests that complex biochemical processes, including the activation of signaling pathways, may underlie Tesamorelin and Mod GRF’s possible interactions with GHRH receptors. Tesamorelin and modified granulocyte-colony stimulating factor (Mod GRF) have been hypothesized to activate intracellular signaling pathways by generating conformational changes in the structure of the GHRH receptor upon engagement. It has also been proposed that Tesamorelin and Modified GRF may boost target cell cyclic adenosine monophosphate (cAMP) synthesis. Activating the adenylate cyclase, which converts ATP to cAMP, might do this. Protein kinase A (PKA) seems to be a critical intracellular signaling molecule, and it is thought that elevated cAMP levels may activate PKA. Possible downstream cellular reactions include phosphorylation of many target proteins. Findings imply that HGH production and secretion from somatotrophs in the pituitary gland may be stimulated by Tesamorelin and Mod GRF’s possible activation of the GHRH receptor and the cAMP-PKA signaling cascade. It has also been purported that the production of insulin-like growth factor-1 (IGF-1) may be influenced by the HGH secreted by pituitary cells. Also, researchers propose that IGF-1 may have a “GH independent growth stimulating effect, which concerning cartilage cells is possibly optimized by the synergistic action with GH.”
Tesamorelin, Mod GRF, and Ipamorelin Pepitde Blend Receptors
Ipamorelin’s suggested mode of action proposes that a combination of Tesamorelin, Modified growth factor receptor, and Ipamorelin may also interact with the GHS receptors. Researchers have hypothesized that Ipamorelin may display selectivity by binding only to the GHS receptor, with little to no cross-reactivity to other receptors. Scientists also purported that “Very surprisingly, Ipamorelin did not release ACTH or cortisol in levels remarkably different from those observed following GHRH stimulation.” Since it seems selective, Ipamorelin may stimulate pituitary cells to secrete growth hormone possibly without causing them to secrete the stress hormones cortisol and adrenocorticotropic hormone (ACTH). Hormones like cortisol and ACTH have been linked to the stress response and are considered to have a wide range of metabolic and immunological consequences.
Investigations propose that Ipamorelin may operate on somatotroph cells in the anterior pituitary gland by connecting with the GHS receptors, potentially activating many intracellular signaling pathways.
Researchers interested in further investigations may buy peptide blends from a trusted online source such as Biotech Peptides.
References
[i] Clinical Review Report: Tesamorelin (Egrifta) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016 Aug. 1, Introduction. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539137/
[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] Johansen, P. B., Nowak, J., Skjaerbaek, C., Flyvbjerg, A., Andreassen, T. T., Wilken, M., & Orskov, H. (1999). Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 9(2), 106–113. https://doi.org/10.1054/ghir.1999.9998
[iv] Spooner, L. M., & Olin, J. L. (2012). Tesamorelin: a growth hormone-releasing factor analogue for HIV-associated lipodystrophy. The Annals of pharmacotherapy, 46(2), 240–247. https://doi.org/10.1345/aph.1Q629
[v] Jiménez-Reina, L., Cañete, R., de la Torre, M. J., & Bernal, G. (2002). Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro. Histology and histopathology, 17(3), 707–714. https://doi.org/10.14670/HH-17.707
