AHK-Cu is often described as a small tripeptide (alanine–histidine–lysine) that may incorporate a copper ion bound to the residues of alanine and histidine.^[1] Some researchers believe that the amino acid sequence might be endogenously occurring. Investigations by qualified researchers also propose that AHK-Cu peptide might have a role in modulating several processes in endothelial cells, such as hair follicle cells, such as growth, differentiation, and programmed cell death.

 

Mechanism of Action

AHK-Cu peptide has been examined for its possible involvement in hair growth and the maintenance of dermal tissue. In some studies, it appears to act on fibroblasts, which are cells that might produce and maintain the extracellular matrix (ECM)—a complex network of proteins, including collagen and elastin, that provides structural support around cells. Fibroblasts may also secrete certain signaling molecules, such as Vascular Endothelial Growth Factor (VEGF). Fibroblasts are typically recognized as cells that may synthesize essential structural proteins, including collagen. VEGF refers to a protein family that may be crucial for forming new blood vessels, a process termed angiogenesis. By increasing VEGF production, AHK-Cu peptide might strengthen blood vessel formation, possibly supporting how nutrients and oxygen are delivered to various tissues, including hair follicles.^[2] This route may be relevant for hair growth, as additional nutrients and oxygen may theoretically support follicle function.

AHK-Cu peptide has also been linked to a possible influence on Transforming Growth Factor Beta 1 (TGF-β1). TGF-β1, sometimes viewed as a critical cytokine, is studied for its role in cell growth, immune regulation, and wound repair. If AHK-Cu peptide happens to lower TGF-β1 levels, it might modify certain cell processes or immune responses, though the extent of this potential remains speculative. Because AHK-Cu peptide contains a copper ion, it might engage in enzymatic pathways that influence collagen and elastin production. Collagen and elastin are ECM proteins that may help maintain skin structure elasticity and structural stability. Copper ions themselves have been explored for possible antioxidant activity, which may mean they scavenge free radicals or support other protective mechanisms in cells.
 

Scientific Research and Studies

 

AHK-Cu Peptide and Hair Follicles

In a recent study ^[3], the researchers examined whether AHK-Cu peptide might influence hair growth in laboratory settings. They observed that this peptide may support the elongation of hair follicles and might also encourage the proliferation of dermal papilla cells (DPCs). DPCs are often viewed as specialized fibroblasts with a suggested capacity to promote hair follicle maturation. The same study additionally proposed that AHK-Cu peptide may reduce the frequency of apoptotic (programmed cell death) DPCs. Subsequent analyses indicated that the peptide might elevate the ratio of Bcl-2 (B-cell lymphoma 2) to Bax (Bcl-2-associated X protein). Bcl-2 is frequently seen as an anti-apoptotic factor that may impede cell death, whereas Bax is thought to be pro-apoptotic and might contribute to cell death pathways.

Investigators further speculated that AHK-Cu peptide might decrease cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) levels—biomolecules often evaluated as markers of cell death. Because a higher Bcl-2/Bax ratio is commonly associated with fewer apoptotic events, the study proposed that such a shift in the ratio may favor cell survival and possibly maintain viable DPC populations. Ultimately, the authors concluded the following: “The present study proposed that AHK-Cu promotes the growth of […] hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis of DPCs.”^[3]

 

AHK-Cu Peptide and Antioxidative Potential

AHK-Cu is frequently mentioned as having strong antioxidant properties, potentially attributable to its distinctive tripeptide structure, which includes alanine, histidine, and lysine, often bound to a copper ion. Based on these purported antioxidant characteristics, some investigations have posited that AHK-Cu peptide may help protect and restore hair follicle size, ultimately increasing hair growth.

Scientists also speculate that AHK-Cu’s antioxidant potential might have broader functions, possibly involving cellular aging, wound repair, and related physiological processes. These observations reflect the notion that AHK-Cu peptide might help protect collagen from oxidative stress and damage. Collagen—a principal protein for upholding tissue integrity—is often viewed as indispensable for dermal layer and hair cell integrity and overall functionality.^[4]

 

AHK-Cu Peptide and Dermal Cells

Preliminary laboratory work has indicated that “AHK-Cu increases the growth and viability of dermal fibroblasts while stimulating the production of collagen.” Observations suggest that, in certain experiments, the presence of AHK peptide alone appeared to promote both fibroblast viability and replication, in addition to supporting the production of collagen type I.

Investigations measuring collagen type I levels after exposing normal dermal fibroblasts to different AHK concentrations suggested a marked rise in collagen synthesis, which was at times documented to be around threefold compared to control groups.^[5] These findings point to the possibility that AHK might help replenish or maintain the extracellular matrix, which comprises various proteins that form the supportive framework of tissues. By theoretically impacting collagen levels in dermal fibroblasts, AHK-Cu peptide might aid dermal layer functionality, although researchers continue to explore the extent of its potential.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing. Bodily introduction of any sort is strictly prohibited by law. All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References:

1. Kapoor R, Shome D, Vadera S, Kumar V, Ram MS. QR678 & QR678 Neo Hair Growth Formulations: A Cellular Toxicity & Animal Efficacy Study. Plast Reconstr Surg Glob Open. 2020 Aug 25;8(8):e2843. doi: 10.1097/GOX.0000000000002843. PMID: 32983753; PMCID: PMC7489598.
2. Sadgrove NJ, Simmonds MSJ. Topical and nutricosmetic products for healthy hair and dermal anti-aging using “dual-acting” (2 for 1) plant-based peptides, hormones, and cannabinoids. FASEB Bioadv. 2021 Jun 6;3(8):601-610. doi: 10.1096/fba.2021-00022. PMID: 34377956; PMCID: PMC8332470.
3. Pyo HK, Yoo HG, Won CH, Lee SH, Kang YJ, Eun HC, Cho KH, Kim KH. The effect of tripeptide-copper complex on human hair growth in vitro. Arch Pharm Res. 2007 Jul;30(7):834-9. doi: 10.1007/BF02978833. PMID: 17703734.
4. Kecel-Gunduza, S., Kocb, E., Bicaka, B., Kokcub, Y., Ozela, A. E., & Akyuzc, S. (2020). IN SILICO ANALYSIS FOR CHARACTERIZING THE STRUCTURE AND BINDING PROPERTIES OF ALA-HIS-LYS (AHK) TRIPEPTIDE. The Online Journal of Science and Technology-July, 10(3).
5. Patt, L. M., & Procyte, A. (2009). Neova® DNA Repair Factor Nourishing Lotion Stimulates Collagen and Speeds Natural Repair Process. skin, 1, 2.

Mechano-growth factor (MGF) is posited to be a short, 24–24-amino-acid segment that may appear within one of the isoforms of insulin-like growth factor-1 (IGF-1).^[1] For context, IGF-1 is widely regarded as one of the most powerful endogenous factors driving cellular growth and proliferation. One of its isoforms produced via the IGF-1 gene appears to be the IGF-IEc (otherwise referred to as full-length MGF) isoform. Once produced, this isoform might be cleaved to generate both mature IGF-I—a 70–amino-acid protein common to all IGF-I isoforms—and a distinct 24–amino-acid peptide termed as “MGF.” The name MGF is based on observations that IGF-IEc gene expression may become upregulated when muscle cells are subjected to mechanical stress (for example, exercise). MGF is also termed MGF-Ct24E, MGF-24aa-E, or E-domain of IGF-1Ec. However, endogenous MGF has not been isolated. In research models like these, scientists have studied only synthetic MGF.^[2]

 

Mechanism of Action

Researchers have posited that MGF may promote muscle cell hypertrophy and repair, but via mechanisms that may differ compared to native IGF-1. IGF-I itself is posited to bind to the IGF-1 receptor on muscle cells and triggers the PI3K–Akt pathway, a signaling route that often promotes cell survival, differentiation, and controlled proliferation. In contrast, several in vitro studies have noted that synthetic MGF does not appear to activate Akt robustly. Instead, they may increase phosphorylation of ERK (particularly ERK5) and support MEF2C activity—two components more strongly linked to gene transcription events that may drive an increase in cellular size, aka hypertrophy.^[1][2] In other words, researchers posit that synthetic MGF seemingly steers the cell toward a gene expression profile that bolsters muscle cell growth in ways that might not precisely mirror the mature IGF-1 response.

 

Scientific Research and Studies

 

MGF and Muscle Cell Survival

Muscle cell damage is typically associated with increased oxidation levels, cellular death, and replacement with fibrotic tissue. A study indicates that MGF appears to reduce fibrosis in injured skeletal muscle cells, possibly by decreasing the synthesis of collagen types I and III.^[3] This reduction in collagen deposition might be mediated by the downregulation of pro-fibrotic cytokines such as TGF-β, which is thought to play a central role in fibrosis. Additionally, MGF may modulate the inflammatory environment within the injured muscle cells. MGF was associated with lowered levels of pro-inflammatory cytokines, including TNF-α, IL-1β, and IFN-γ, suggesting that MGF might help attenuate excessive inflammatory responses that might otherwise impair recovery of muscular tissue. Furthermore, MGF potentially affects oxidative stress within the injured tissue. The study found that MGF led to a decrease in the expression of gp91phox, a key subunit of NADPH oxidases involved in the production of reactive oxygen species (ROS). By reducing oxidative stress, MGF may create a more favorable environment for muscle cell survival and tissue repair. Additionally, MGF might influence extracellular matrix (ECM) remodeling by modulating the expression of matrix metalloproteinases (MMPs). MGF was associated with altered levels of various MMPs, which are involved in the degradation and remodeling of the ECM. This modulation of MMP activity may contribute to a balanced ECM environment, facilitating muscular tissue recovery and mitigating excessive fibrosis.

 

MGF and Muscle Cell Development

It is posited that MGF might support the activation and proliferation of satellite cells, which are essential for the growth and repair of muscular tissue.^[4] By potentially delaying the onset of replicative senescence, MGF may extend the proliferative lifespan of these precursor cells. This delay in senescence may be mediated through the regulation of cell cycle proteins or by modulating stress response pathways, such as the p16 pathway, which scientists believe may have some impact on cell cycle arrest. Additionally, MGF appears to promote the fusion of myoblasts into myotubes, leading to hypertrophy. This hypertrophic potential might be achieved by recruiting reserve cells—those that typically remain quiescent and undifferentiated—to participate in myotube formation. By reducing the population of reserve cells, MGF may facilitate an increase in the number of nuclei per myotube. It might even support the synthesis of contractile proteins like myosin heavy chain (MyHC). These actions suggest that MGF might play a role in optimizing the balance between cell proliferation and differentiation, thereby supporting muscular tissue maintenance and adaptation.

 

MGF and Cardiac Cell Survival

MGF has been posited to exert anti-apoptotic potential and facilitate the recruitment of stem cells, which are crucial for cardiac tissue repair.^[5] One proposed mechanism is MGF’s ability to inhibit apoptosis in cardiac myocytes. The research indicates that MGF may reduce cell death in myocytes subjected to hypoxic conditions. This protective potential appears to be associated with an increase in Bcl-2 gene expression, a protein suggested to play a role in mitigating apoptosis. The study suggests that MGF might support cell survival by modulating apoptotic pathways, potentially through the upregulation of anti-apoptotic factors like Bcl-2.

MGF is thought to be potentially involved in the recruitment and migration of stem cells to the site of cardiac cell injury. The encapsulated MGF within the microrods was observed to increase the migration of mesenchymal stem cells (hMSCs) in vitro. This chemotactic activity of MGF may create a favorable microenvironment for stem cell homing, which is essential for tissue regeneration and repair. The mechanism behind this may involve MGF interacting with the IGF-1 receptor and activating downstream signaling pathways such as Erk1/2, which are implicated in cell migration and survival.

 

MGF and Muscular Tissue Fiber Thickness

Researchers have commented that full-length MGF may have “resulted in a 25% increase in the mean muscle fiber cross-sectional area” in experimental settings.^[6] The researchers posit that full-length MGF might engage similar signaling pathways as IGF-I, which is believed to coordinate myoblast proliferation, differentiation, and fiber formation in muscular tissue. The comparable maximal activation of IGF-IR by MGF at high concentrations indicates that, under certain conditions, MGF may potentially interact with the growth of muscular tissue akin to IGF-I. Additionally, full-length MGF was found to activate the insulin receptors IR-A and IR-B. The activation of IR-A by MGF reached levels similar to those induced by insulin at high concentrations, while IR-B stimulation by MGF was even more pronounced. This dual receptor activation posits that MGF may influence multiple signaling cascades involved in hypertrophy and repair of muscular tissue. The hypothetically better-supported stimulation of IR-B suggests a possible role for MGF in modulating metabolic and growth-related pathways that contribute to increased fiber size in muscular tissue. However, the truncated version of MGF may not have a similar potential

 

MGF and Bone Cell Proliferation

In experimental models involving bone defects, MGF was apparently associated with accelerated healing, which might be attributed to its potential to promote osteoblast activity and proliferation. This accelerated healing might result from better-supported cellular processes that support bone regeneration and remodeling. The potential mechanisms by which MGF influences bone cells and tissues appear to involve several intricate cellular pathways.

Primarily, MGF is believed to support the proliferation of osteoblast-like cells, as supported by data collected by observing the cells and their hypothesized ability to increase cell growth more than IGF-1. However, the researchers also noted that the “peptide actions were independent of IGF-IR signaling,” suggesting an alternative proliferative potential. This pro-proliferative potential might be mediated through the modulation of the cell cycle, where MGF possibly induces an accumulation of cells in the S and G2/M phases. Such cell cycle alterations suggest that MGF may even facilitate DNA synthesis and promote entry into mitosis, which may hypothetically support increased cell division.

 

MGF and Cartilage Cells

Some researchers suggest that MGF might regulate chondrocyte proliferation and migration.^[7] Studies indicate that MGF may support the mobility of mesenchymal stem cells (MSCs) and chondrocytes, possibly facilitating their recruitment to injury sites. This migration may be mediated through the activation of the RhoA/Yes-associated protein (YAP) signaling pathway, which is involved in cytoskeletal reorganization and cell movement. By promoting focal adhesion formation and cytoskeleton stability, MGF may help chondrocytes navigate the damaged environment to participate in tissue repair.

Additionally, MGF may influence chondrocyte differentiation and extracellular matrix (ECM) production. In the presence of transforming growth factor-beta 3 (TGF-β3), MGF appears to accelerate the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes, potentially supporting the synthesis of type II collagen (Col2) and aggrecan, key components of the cartilage ECM. This action might be linked to the activation of the extracellular signal-regulated kinase (ERK) pathway, which is associated with cellular differentiation processes.

MGF also appears to play some kind of role in modulating inflammatory responses and apoptosis within cartilage tissue. It may reduce the expression of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), thereby potentially alleviating inflammation-induced cartilage degradation. Furthermore, MGF might inhibit apoptotic pathways by downregulating proteins like Bax and caspase-3 while upregulating Bcl-2, which may help preserve chondrocyte viability in stressful environments. The interaction of MGF with signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt and ERK/MAPK suggests it may help maintain cartilage homeostasis by promoting ECM synthesis and inhibiting catabolic processes.

The exact outcomes of these pathway activations appear to be context-dependent, varying between normal and damaged cartilage conditions. For instance, while PI3K/Akt signaling is generally associated with anabolic activities in functional cartilage, its role in damaged tissue is believed to potentially involve complex regulatory actions that are not yet fully understood. Moreover, MGF’s ability to induce the unfolded protein response (UPR) through pathways like protein kinase RNA-like ER kinase (PERK) indicates a potential role in managing cellular stress within chondrocytes. By influencing UPR-related proteins such as glucose-regulated protein 78 (GRP78), MGF may help chondrocytes adapt to hypoxic or mechanically stressful environments, thereby supporting their survival and function.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing. Bodily introduction of any sort is strictly prohibited by law. All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References:

1. Li C, Vu K, Hazelgrove K, Kuemmerle JF. Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn’s disease and smooth muscle hypertrophy. Am J Physiol Gastrointest Liver Physiol. 2015 Dec 1;309(11):G888-99. doi: 10.1152/ajpgi.00414.2014. Epub 2015 Oct 1. PMID: 26428636; PMCID: PMC4669353.
2. Matheny RW Jr, Nindl BC, Adamo ML. Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 2010 Mar;151(3):865-75. doi: 10.1210/en.2009-1217. Epub 2010 Feb 3. PMID: 20130113; PMCID: PMC2840678.
3. Liu X, Zeng Z, Zhao L, Chen P, Xiao W. Impaired Skeletal Muscle Regeneration Induced by Macrophage Depletion Could Be Partly Ameliorated by MGF Injection. Front Physiol. 2019 May 17;10:601. doi: 10.3389/fphys.2019.00601. PMID: 31164836; PMCID: PMC6534059.
4. Kandalla PK, Goldspink G, Butler-Browne G, Mouly V. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011 Apr;132(4):154-62. doi: 10.1016/j.mad.2011.02.007. Epub 2011 Feb 25. PMID: 21354439.
5. Doroudian G, Pinney J, Ayala P, Los T, Desai TA, Russell B. Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014 Oct;16(5):705-15. doi: 10.1007/s10544-014-9875-z. PMID: 24908137; PMCID: PMC4418932.
6. Janssen JA, Hofland LJ, Strasburger CJ, van den Dungen ES, Thevis M. Potency of Full-Length MGF to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations. PLoS One. 2016 Mar 18;11(3):e0150453. doi: 10.1371/journal.pone.0150453. PMID: 26991004; PMCID: PMC4798685.
7. Liu Y, Duan M, Zhang D, Xie J. The role of mechano growth factor in chondrocytes and cartilage defects: a concise review. Acta Biochim Biophys Sin (Shanghai). 2023 May 12;55(5):701-712. doi: 10.3724/abbs.2023086. PMID: 37171185; PMCID: PMC10281885.

Adipotide, also referred to as FTPP or Prohibitin-targeting peptide 1 (Prohibitin-TP01), is a synthetic compound that may mimic specific parts of endogenously occurring proteins. In other words, it is posited to be a “peptidomimetic,” which means it may produce sequences of amino acids to imitate the way certain proteins normally work. The sequence of the peptide is GKGGRAKDC-GG-D(KLAKLAK)2. While scientific understanding is still incomplete, researchers posit that Adipotide’s unique nine-amino-acid segment (CKGGRAKDC) may be drawn to a receptor system involving two proteins, annexin A2 (ANXA2) and prohibitin (PHB).^[1]

Scientists believe that these two proteins function primarily as targets that help direct the Adipotide molecule to specific cells. Specifically, each of them appears to be present in different cells. Still, they are posited to form a unique ANXA2-PHB receptor system only found in white fat tissue, thus allowing for precise targeting.^[2] The remaining segment (KLAKLAK)₂ is believed to interfere with the function of mitochondria—the energy-producing parts of cells. Adipotide is posited to impede their function, leading to cell death. Early studies suggest that Adipotide FTPP may act mostly on white adipose tissue (WAT) cells, but the broader implications remain areas of ongoing research.

 

Mechanism of Action

ANXA2 and PHB are often found on endothelial cells in blood vessels connected to cells like fat cells (adipocyte-like cells) grown under laboratory conditions. Although the exact mechanisms are not fully understood, one component of Adipotide FTPP, also referred to by researchers as the CKGGRAKDC motif, may bind to these receptor complexes. After the peptide is taken up into the cell, another segment—called the (KLAKLAK)₂ domain—may compromise the integrity of the membranes of the mitochondria of endocrine cells, which may trigger processes leading to cell death (apoptosis). This process is posited to lead to the reduction or destruction of the adipose vasculature, which in turn might influence the local adipose microenvironment.

Through this process, researchers believe that Adipotide FTPP may contribute to some level of reduction in the vascular network that nourishes white adipose tissue, ultimately resulting in diminished adipose mass.^[3] Furthermore, the binding of the peptide to the receptors might influence the positioning and activity of proteins involved in transporting fatty acids, such as CD36, potentially affecting how these cells take in and process fats. Specifically, researchers posit that a “biochemical interaction between ANX2 and PHB regulates CD36-mediated fatty acid transport in WAT, thus revealing a new potential pathway for intervention in metabolic diseases.”^[4] Thus, by interfering with the normal partnership between ANXA2 and PHB, Adipotide FTPP might reduce the efficiency with which fatty acids enter adipocyte-like cells.

 

Scientific Research and Studies

 

Adipotide FTPP and Fat Cells Metabolism

Laboratory investigations in different models indicate that targeting the vascular supply may induce notable reductions in white adipose mass.^[5] Over a few weeks of experimentation, the researchers were able to produce imaging-based assessments such as DEXA scanning and MRI and have apparently observed a total adiposity reduction of approximately 38.7%, including localized decreases that may range from around 17.5% to 27.0%. Such changes may be related to a diminished capillary network that potentially limits nutrient and oxygen delivery to adipose compartments. This may hinder the survival and maintenance of cells like these.

Early evaluations further suggest that shifts in metabolic parameters might accompany these vascular alterations. It remains unclear whether these outcomes arise directly from the reduced vascular supply or from more complex signaling feedback originating within the disrupted adipose milieu, where metabolic intermediaries or hormonal cues might adjust in response to the altered environment. The researchers also commented that the apparent “weight loss is also accompanied by a modest reduction in serum-free fatty acids and an improvement in insulin resistance.”

 

Adipotide FTPP and Energy Intake

In controlled laboratory settings, murine models exposed to Adipotide FTPP apparently displayed considerable fat mass reduction when on high-fat diets. Still, the same was not true for murine research models on low-fat diets.^[6] This difference may be related to the expanded adipose compartment in high-fat–fed models, which possibly provides a more substantial vascular target. Moreover, during several days of exposure to Adipotide FTPP directed at white adipose vasculature, observation of these research models indicated a progressive decrease in caloric intake that was not immediately obvious at the initiation of the experimentation but occurred after some delay.

Such a delay in reduced consumption may indicate that the targeted apoptotic process requires some time to influence downstream metabolic or behavioral signals. Although leptin levels, typically associated with suppression of hunger hormone signals, appeared reduced along with fat mass, the researchers posit that the diminished nutrient supply and possible adipose-derived signals might have overridden the usual compensatory hyperphagic response expected from lower circulating leptin.

 

Adipotide FTPP and Insulin Resistance Models

Through the destruction of these vascular cells, there is potentially a reduction in nutrient and oxygen delivery to the adipose tissue itself, which may lead to fewer and possibly smaller adipocytes. Researchers suggest that this vascular targeting apparently results in reprogramming of metabolic pathways, as indicated by altered expression profiles of genes involved in mitochondrial processes, oxidative phosphorylation, and branched-chain amino acid degradation.^[7] Such transcriptional shifts may potentially restore or at least partly normalize adipose tissue function that had been disrupted in the context of excess adiposity. In controlled laboratory work with murine models, the peptide’s influence on circulating lipids and metabolites suggests that it may decrease reliance on fatty acid oxidation and instead promote glucose utilization.

Altered levels of various metabolites, including a range of fatty acids and acylcarnitines, might reflect a metabolic state more conducive to better-supported glucose regulation. Although the exact details remain uncertain, the peptide may restore a more favorable metabolic profile within adipose tissue. Something like this may potentially contribute to the reversal of some of the mitochondrial and metabolic impairments that develop during exposure to high-fat conditions. At the same time, the peptide’s potential influence on macrophage-related gene expression hints at subtle immunological shifts in the adipose environment, though the implications for these changes remain unclear.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing. Bodily introduction of any sort is strictly prohibited by law. All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References:

1. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004 Jun;10(6):625-32. doi: 10.1038/nm1048. Epub 2004 May 9. PMID: 15133506.
2. Staquicini FI, Cardó-Vila M, Kolonin MG, Trepel M, Edwards JK, Nunes DN, Sergeeva A, Efstathiou E, Sun J, Almeida NF, Tu SM, Botz GH, Wallace MJ, O’Connell DJ, Krajewski S, Gershenwald JE, Molldrem JJ, Flamm AL, Koivunen E, Pentz RD, Dias-Neto E, Setubal JC, Cahill DJ, Troncoso P, Do KA, Logothetis CJ, Sidman RL, Pasqualini R, Arap W. Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18637-42. doi: 10.1073/pnas.1114503108. Epub 2011 Nov 2. PMID: 22049339; PMCID: PMC3219136.
3. Hossen N, Kajimoto K, Akita H, Hyodo M, Harashima H. A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication. J Control Release. 2013 Oct 28;171(2):104-12. doi: 10.1016/j.jconrel.2013.07.013. Epub 2013 Jul 18. PMID: 23871959.
4. Salameh A, Daquinag AC, Staquicini DI, An Z, Hajjar KA, Pasqualini R, Arap W, Kolonin MG. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue. JCI Insight. 2016 Jul 7;1(10):e86351. doi: 10.1172/jci.insight.86351. PMID: 27468426; PMCID: PMC4959783.
5. Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, Pasqualini R. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011 Nov 9;3(108):108ra112. doi: 10.Doi6/scitranslmed.3002621. PMID: 22072637; PMCID: PMC3666164.
6. Kim DH, Woods SC, Seeley RJ. Peptide is designed to elicit apoptosis in adipose tissue endothelium and reduce food intake and body weight. Diabetes. 2010 Apr;59(4):907-15. doi: 10.2337/db09-1141. Epub 2010 Jan 26. PMID: 20103704; PMCID: PMC2844838.
7. Kim DH, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, Newgard CB, Woods SC, Seeley RJ. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes. 2012 Sep;61(9):2299-310. doi: 10.2337/db11-1579. Epub 2012 Jun 25. PMID: 22733798; PMCID: PMC3425411.

Tesamorelin is a synthetic peptide composed of 44 amino acids designed to closely mimic the structure and function of growth hormone-releasing hormone (GHRH). Modifications to its structure, particularly at the N- and C-termini, are believed to support its stability and resistance to enzymatic degradation compared to endogenous GHRH. These changes include the addition of an acetyl group at the N-terminus and a trans-3-hexenoic acid group at the C-terminus.

Adjustments like these aim to support the peptide’s biological activity while maintaining its compatibility with GHRH receptors. The full chemical designation of Tesamorelin, N-(trans-3-hexenoyl)-[Tyr1]hGRF(1–44)NH₂ acetate, highlights these specific modifications.

Tesamorelin is thought to interact with GHRH receptors located on somatotroph cells in the anterior pituitary gland, which is believed to contribute to the triggering of a series of cellular responses. This interaction is believed to help activate adenylate cyclase, an enzyme responsible for converting adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). Increased cAMP levels might activate protein kinase A (PKA), which phosphorylates target proteins, which may potentially initiate activation of signaling pathways that support the secretion of growth hormone (GH). GH released into the circulation may stimulate hepatocytes to produce insulin-like growth factor-1 (IGF-1), a key mediator of GH’s anabolic impacts.^[2]

Additionally, GH may also promote local IGF-1 production within tissues. IGF-1 is thought to play a critical role in cellular growth and survival. At the same time, GH itself may exhibit lipolytic activity, targeting adipose tissue depots such as visceral and abdominal fat to facilitate fat breakdown. Research suggests that Tesamorelin likely increases GH secretion significantly, with studies reporting a 69% rise in overall GH levels (measured by the area under the curve) and a 55% increase in the average GH pulse area. These impacts are said to be accompanied by a notable 122% elevation in IGF-1 levels. However, Tesamorelin appears not to affect the frequency or peak amplitude of GH pulses, indicating a specific modulation of GH dynamics.^[3]

 

Scientific and Research Studies

 

Tesamorelin Peptide and Hepatic Fat Fraction in Immunocompromised Models

Research suggests that severe immunodeficiency may contribute to the onset of non-alcoholic fatty liver disease (NAFLD), with clinical data suggesting a prevalence of nearly 40% among HIV-positive populations.^[4]

In a controlled study^[5], 61 HIV-positive research models exhibiting elevated hepatic fat fractions (HFF) were enrolled to evaluate the impacts of Tesamorelin compared to a placebo over 12 months. Participants were randomized to receive either Tesamorelin or a placebo, with HFF monitored at the study’s conclusion. After 12 months, findings suggested that 35% of subjects introduced with Tesamorelin exhibited a reduction in HFF of less than 5%, while only 4% of subjects in the placebo group indicated similar reductions. Importantly, there was no reported impact on glucose levels in either group, suggesting Tesamorelin’s impacts on HFF may be independent of glycemic modulation.

 

Tesamorelin Peptide and Lipid Metabolism Disorders

Lipodystrophy refers to pathological conditions characterized by abnormal fat distribution and metabolism. This condition manifests as a loss of fat in specific regions and excessive fat accumulation in others. Metabolic disturbances, including insulin resistance and elevated cholesterol and triglyceride levels, often accompany these abnormalities. In experimental models of lipodystrophy, researchers have reportedly observed reduced levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Researchers exploring Tesamorelin hypothesize that this peptide may positively influence lipid metabolism, particularly in lipodystrophy-associated disorders.

A clinical study consisting of two phase III trials researched Tesamorelin’s impacts over 52 weeks in 806 research models presenting with immunodeficiency and lipodystrophy. The trials were structured into two phases. In the first phase, participants were randomized into two groups: 543 subjects received Tesamorelin, and 263 subjects were given a placebo for 26 weeks. During the second phase, subjects in the Tesamorelin group were further randomized, with one subgroup continuing Tesamorelin and the other switching to a placebo for an additional 26 weeks.

At the 26-week evaluation, it was reported that individuals introduced to Tesamorelin likely exhibited a substantial reduction in visceral adipose tissue (VAT) levels, averaging a 15.4% decrease compared to baseline measurements. Additionally, this group reportedly demonstrated significant reductions in serum triglycerides and cholesterol levels compared to the placebo cohort. Based on this reported outcome, scientists suggest that “treatment with Tesamorelin reduces VAT and maintains the reduction for up to 52 weeks, preserves abdominal subcutaneous adipose tissue, [improves] image and lipids, and is overall well tolerated without clinically meaningful changes in glucose parameters.”

 

Tesamorelin Peptide and Insulin Sensitivity

A randomized clinical trial^[7] was conducted aiming to explore the potential role of Tesamorelin in modifying insulin sensitivity in individuals with Type II diabetes. The study, conducted over 12 weeks, involved 53 participants divided into three groups: two receiving varying concentrations of Tesamorelin and one receiving a placebo. Researchers measured fasting glucose levels, glycosylated hemoglobin (HbA1c), and diabetes control metrics to assess any significant changes attributable to Tesamorelin introduction.

At the conclusion of the trial, the data results suggested no statistically significant differences in these parameters among the three groups. Both fasting glucose and HbA1c levels, as well as overall diabetes management outcomes, appeared unaffected by Tesamorelin introduction. These findings suggest that Tesamorelin may not exert a measurable impact on insulin sensitivity or glucose regulation in this specific population under the conditions tested.

 

Tesamorelin Peptide and Neurocognitive Function

In a clinical trial investigating Tesamorelin’s potential impact on cognitive function^[8], immunodeficient models exhibiting mild cognitive impairment were evaluated. The primary objective of this study was to assess the impacts of Tesamorelin on neurological functioning. A total of 100 participants were enrolled in the trial. The study design included a daily introduction to Tesamorelin for 6 months, followed by a 6-month washout phase where no Tesamorelin was administered.

After the washout phase, Tesamorelin was reintroduced once daily for an additional 6 months. The primary outcome measure was reported changes in neurocognitive performance, including “change in IGF-1, magnetic resonance spectroscopy measures of brain inflammation/immune activation and hippocampal volume,” assessed using the Global Deficit Score (GDS) at the 6- and 12-month time points including.

 

Tesamorelin Peptide and Muscular Tissue Modulation

A study investigating the potential impacts of Tesamorelin on muscular tissue structure employed computed tomography (CT) imaging to assess changes in muscular tissue density and volume.^[9] CT, which integrates X-ray imaging with advanced computer technology, allows for high-resolution visualization of internal structures. The study’s findings suggested a potential association between Tesamorelin and better-supported muscular tissue quality, specifically in terms of increased muscular tissue density and volume.

Notable variations in groups of muscular tissue, such as the rectus abdominis and paraspinal muscular tissue, including an increase in muscular tissue density and volume, as well as a reduction in fat content, were all reportedly observed in the Tesamorelin group when compared to a placebo control group. Based on this, researchers suggest that “Tesamorelin was effective in increasing skeletal muscle area and density among those with a clinically significant decrease in visceral adipose tissue on treatment.”^[9]

 

Tesamorelin Peptide and Visceral Fat Reduction

Visceral obesity is a condition characterized by excessive fat accumulation around internal organs. The condition is often observed by researchers studying lipodystrophy models, and is said to be linked to several metabolic disorders, including insulin resistance, hyperlipidemia, and atherosclerosis. These conditions are believed to potentially contribute to significant complications in metabolic function, including elevated blood glucose levels, increased LDL cholesterol, and hyperuricemia.

Research into Tesamorelin suggests that the peptide may reduce visceral fat by up to 25% in models of lipodystrophy.^[10] This reduction may suggest that Tesamorelin might play a role in mitigating some of the metabolic disturbances associated with visceral fat accumulation, presenting a promising therapeutic avenue for addressing visceral obesity-related metabolic disorders.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing. Bodily introduction of any sort is strictly prohibited by law. All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References:

1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Tesamorelin. https://www.ncbi.nlm.nih.gov/books/NBK548730/
2. Stanley TL, Chen CY, Branch KL, Makimura H, Grinspoon SK. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. J Clin Endocrinol Metab. 2011 Jan;96(1):150-8. doi: 10.1210/jc.2010-1587. Epub 2010 Oct 13. PMID: 20943777; PMCID: PMC3038486. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038486/
3. Ferdinandi ES, Brazeau P, High K, Procter B, Fennell S, Dubreuil P. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analog. Basic Clin Pharmacol Toxicol. 2007 Jan;100(1):49-58. doi: 10.1111/j.1742-7843.2007.00008.x. PMID: 17214611. https://pubmed.ncbi.nlm.nih.gov/17214611/
4. Tesamorelin Effects on Liver Fat and Histology in HIV. https://clinicaltrials.gov/ct2/show/NCT02196831
5. Stanley, T. L., Fourman, L. T., Feldpausch, M. N., Purdy, J., Zheng, I., Pan, C. S., Aepfelbacher, J., Buckless, C., Tsao, A., Kellogg, A., Branch, K., Lee, H., Liu, C. Y., Corey, K. E., Chung, R. T., Torriani, M., Kleiner, D. E., Hadigan, C. M., & Grinspoon, S. K. (2019). Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomized, double-blind, multicentre trial. The lancet. HIV, 6(12), e821–e830. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981288/
6. Falutz J, Mamputu JC, Potvin D, Moyle G, Soulban G, Loughrey H, Marsolais C, Turner R, Grinspoon S. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-masked placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010 Sep;95(9):4291-304. doi: 10.1210/jc.2010-0490. Epub 2010 Jun 16. PMID: 20554713. https://pubmed.ncbi.nlm.nih.gov/20554713/
7. Clemmons, D. R., Miller, S., & Mamputu, J. C. (2017). Safety and metabolic effects of tesamorelin, a growth hormone-releasing factor analog, in patients with type 2 diabetes: A randomized, placebo-controlled trial. PloS one, 12(6), e0179538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472315/
8. Phase II Trial of Tesamorelin for Cognition in Aging HIV-Infected Persons. https://clinicaltrials.gov/ct2/show/record/NCT02572323
9. Adrian S, Scherzinger A, Sanyal A, Lake JE, Falutz J, Dubé MP, Stanley T, Grinspoon S, Mamputu JC, Marsolais C, Brown TT, Erlandson KM. The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV. J Frailty Aging. 2019;8(3):154-159. doi: 10.14283/jfa.2018.45. PMID: 31237318; PMCID: PMC6766405. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766405/
10. Sivakumar T, Mechanic O, Fehmie DA, Paul B. Growth hormone axis treatments for HIV-associated lipodystrophy: a systematic review of placebo-controlled trials. HIV Med. 2011 Sep;12(8):453-62. doi: 10.1111/j.1468-1293.2010.00906.x. Epub 2011 Jan 25. PMID: 21265979. https://pubmed.ncbi.nlm.nih.gov/21265979/

GHRP-2 and Ipamorelin are research peptides that are commonly referred to as growth hormone secretagogues (GHSs). This is because they both have the potential to interact with a specific subset of receptors in pituitary gland cells, which are called growth hormone secretagogue receptors. As evident from the name of the receptors, their activation may trigger the release of growth hormone from the anterior pituitary cells. These receptors are different from the GHRH receptors, which are normally activated by the GHRH hormone and are considered to be the main endogenous receptors that play a role in endogenous growth hormone production. Here are more details about the structure and peculiarities of each peptide:

• GHRP-2 refers to “growth hormone-releasing peptide-2“, and it is a hexapeptide.^[1] This compound is categorized within the broader group of GHRPs, which is said to be synthesized from endogenously occurring molecules referred to as met-enkephalins. However, GHRPs do not appear to interact with the receptors for met-enkephalin; instead, they interact with the GHS receptors. GHRP-2 appears to be a non-selective agonist of these receptors. Therefore, it potentially affects growth hormone production in the pituitary gland and possibly modulates the activity of other pituitary-derived hormones.
• Ipamorelin, sometimes identified by the designation NNC 26-0161, is described as a pentapeptide and may be represented by the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2.^[2] Classified as a GHRP and GHS, Ipamorelin is commonly thought to be more selective for stimulating growth hormone secretion, potentially causing less influence on non-growth hormone pituitary hormones compared to other members of this peptide family. Researchers have commented that “ipamorelin did not release ACTH or cortisol in levels significantly different from those observed following GHRH stimulation.”

 

Mechanisms of Action

Ipamorelin and GHRP-2, though structurally distinct, may nonetheless engage with similar underlying biological processes. Both peptides may potentially act on a specific subset of pituitary receptors, often referred to as ghrelin receptors or growth hormone secretagogue receptor 1a (GHS-R1a), which might generally respond to the hormone ghrelin. Upon their proposed interaction with GHS-R1a, these compounds may induce subtle receptor conformational changes that might trigger a sequence of intricate intracellular signaling pathways.^[3] Within these pathways, phospholipase C (PLC) may serve as a key enzyme, as some researchers suspect it might promote the formation of second messengers, such as inositol triphosphate (IP3) and diacylglycerol (DAG).

If these messengers are indeed produced, IP3 might facilitate the controlled release of calcium ions (Ca2+) from internal stores, and DAG may potentially contribute to the activation of protein kinase C (PKC). This enzyme family might influence various cellular functions. The combined action of increased intracellular calcium and possible PKC activation may, in turn, modulate the transcription of genes believed to be involved in growth hormone production and secretion.

 

Scientific and Research Studies

 

Ipamorelin & GHRP-2 Blend and Growth Hormone Signaling

While conclusive data remain scarce, early investigations into GHRP-2 and Ipamorelin may provide some preliminary insights into their potential influence on pituitary cells and their ability for growth hormone synthesis. Growth hormone is considered to be a hormone that has a combination of anabolic and catabolic properties. These properties are of significant research interest to researchers in different fields. Notably, its anabolic properties are considered to be mediated by another mediator called insulin-like growth factor-1 (IGF-1). Consequently, by upregulating growth hormone synthesis, GHRP-2 and Ipamorelin may also upregulate IGF-1. Here are some of the most notable early investigations into GHRP-2 and Ipamorelin potential:

• Studies into GHRP-2 suggest that it might upregulate growth hormone release from anterior pituitary cells by as much as 181 times above the levels measured before exposure to the peptide.^[4] Preliminary data also indicates that mean IGF-1 concentrations might rise by about 80% following exposure to GHRP-2. Another study comparing GHRP-2 to placebo suggested an almost 6-fold higher peak increase in growth hormone synthesis from pituitary cells.^[5]
• In studies examining Ipamorelin, preliminary data imply that growth hormone synthesis may spike substantially, potentially reaching nearly 27 nanograms per milliliter (ng/ml), which is over 60 times greater than the typical 0.4 ng/ml values observed in placebo experiments.^[6]

 

Ipamorelin & GHRP-2 Blend in Muscle Cell Hypertrophy

GHRP-2 and Ipamorelin have both been examined for their possible roles in promoting muscle cell hypertrophy—an increase in the size of muscle cells. This hypertrophy is thought to be associated with increases in growth hormone and IGF-1, both of which can potentially induce anabolic processes. For example, some investigators have hypothesized that GHRP-2, under certain experimental conditions, might influence muscular tissue protein metabolism in a manner that might favor protein synthesis over degradation. In one study conducted on yaks (Bos grunniens), it was proposed that GHRP-2 may have supported muscular tissue protein building through pathways that potentially support protein synthesis rates.^[7] Notably, the researchers commented that “GHRP-2 … muscle protein deposition mainly by up-regulating the protein synthesis pathways”. However, this possibility was considered within the context of experimental models facing limited nutrient availability, challenging environmental conditions, and disease-related stressors, where atrophy may prevail.

The researchers speculated that GHRP-2 might have also contributed to minimizing muscular tissue atrophy in these challenging settings. Similarly, Ipamorelin has been speculated to slow the loss of muscle cells in models of muscular tissue wasting, possibly by indirectly affecting IGF-1 levels in muscular tissues. Some preliminary data suggests that Ipamorelin might mitigate muscular tissue wasting in scenarios involving high corticosteroid levels, as corticosteroids can often promote muscular tissue breakdown.^[8] The underlying processes may be linked to IGF-1-mediated downregulation of enzymes referred to as E3 ubiquitin ligases—including atrogin-1 and MuRF1 (muscle ring finger protein-1)—both of which are commonly associated with protein breakdown in muscle cells. Both peptides may upregulate anabolic signals like IGF-1 that reduce the activity of atrogin-1 and MuRF1, thereby possibly diminishing the pace of protein degradation within muscle cells.^[9]

 

Ipamorelin & GHRP-2 Blend in Bone Tissues

Ipamorelin has been investigated for its potential influences on bone tissues, including possible actions on the formation of new bone and the overall amount of mineral content within skeletal structures. Observations in certain experimental models have hinted that Ipamorelin may contribute to a relative rise in bone mineral content (BMC), which refers to the total mineral content in bone.^[10,11] According to the observations, Ipamorelin exposure was associated with potential increases in bone size, weight, and BMC, although the underlying mechanisms were not fully understood.

The interpretation of such findings is tentative, as the volumetric bone mineral density (BMD) did not consistently increase in parallel. Instead, it appeared that any observed rise in BMC might have stemmed from changes in bone geometry rather than a uniform elevation in mineral density. Although not firmly established, Ipamorelin’s role in possibly stimulating GH and IGF-1 signaling pathways may be one explanation for these skeletal changes. Adding GHRP-2 may theoretically intensify these processes, but at present, data remains limited.

 

Ipamorelin & GHRP-2 Blend and Hunger Hormone Signaling

Apart from interacting with the GHS-R1a in the pituitary gland cells, GHRPs like GHRP-2 and Ipamorelin have also been suggested to interact with the same receptors in other cells, similarly to the interaction of the endogenous hunger hormone ghrelin. Therefore, these peptides are thought to mediate a similar appetite-promoting signaling as ghrelin. In fact, activating these receptors in certain neurons can influence the production of neuropeptides involved in appetite regulation, such as neuropeptide Y (NPY) and agouti-related peptide (AgRP). These neuropeptides are commonly associated with increasing appetite. Activating the GHS-R1a may also mediate the suppression of alpha-melanocyte-stimulating hormone (α-MSH), which usually reduces appetite.

Experiments with GHRP-2 and Ipamorelin also seem to suggest that. For example, there was a study in laboratory models where Ipamorelin-exposed subjects appeared to experience measurable increases in food intake and overall mass, possibly including a rise in adipose (fat) tissue, on the order of roughly 15%.^[12] According to another group of researchers, GHRP-2 exposure was also suggested to increase food consumption by approximately 36% compared to controls, potentially translating to higher energy intake per unit of mass. The energy consumption was reposted to increase to 136.0±13.0 kilojoules per kilogram, as opposed to 101.3±10.5 kilojoules per kilogram in controls.^[13] Although the biological mechanisms remain incompletely characterized, these findings raise the possibility that Ipamorelin and GHRP-2 may modulate energy balance and physical composition through a combination of influencing anabolic signaling and hunger hormone signaling.

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing. Bodily introduction of any sort is strictly prohibited by law. All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References:

1. Berlanga-Acosta J, Abreu-Cruz A, Herrera DGB, Mendoza-Marí Y, Rodríguez-Ulloa A, García-Ojalvo A, Falcón-Cama V, Hernández-Bernal F, Beichen Q, Guillén-Nieto G. Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects. Clin Med Insights Cardiol. 2017 Mar 2;11:1179546817694558. doi: 10.1177/1179546817694558. PMID: 28469491; PMCID: PMC5392015.
2. Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998 Nov;139(5):552-61. doi: 10.1530/eje.0.1390552. PMID: 9849822.
3. Jiménez-Reina L, Cañete R, de la Torre MJ, Bernal G. Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro. Histol Histopathol. 2002;17(3):707-14. doi: 10.14670/HH-17.707. PMID: 12168778.
4. Veldhuis, J. D., Keenan, D. M., Bailey, J. N., Adeniji, A. M., Miles, J. M., & Bowers, C. Y. (2009). Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp. The Journal of clinical endocrinology and metabolism, 94(6), 2137–2143. https://doi.org/10.1210/jc.2009-0136
5. Bowers, C. Y., Granda, R., Mohan, S., Kuipers, J., Baylink, D., & Veldhuis, J. D. (2004). Sustained elevation of pulsatile growth hormone (GH) secretion and insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and IGFBP-5 concentrations during 30-day continuous subcutaneous infusion of GH-releasing peptide-2 in older men and women. The Journal of clinical endocrinology and metabolism, 89(5), 2290–2300. https://doi.org/10.1210/jc.2003-031799
6. Gobburu, J. V., Agersø, H., Jusko, W. J., & Ynddal, L. (1999). Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical research, 16(9), 1412–1416. https://doi.org/10.1023/a:1018955126402
7. Hu R, Wang Z, Peng Q, Zou H, Wang H, Yu X, Jing X, Wang Y, Cao B, Bao S, Zhang W, Zhao S, Ji H, Kong X, Niu Q. Effects of GHRP-2 and Cysteamine Administration on Growth Performance, Somatotropic Axis Hormone and Muscle Protein Deposition in Yaks (Bos grunniens) with Growth Retardation. PLoS One. 2016 Feb 19;11(2):e0149461. doi: 10.1371/journal.pone.0149461. PMID: 26894743; PMCID: PMC4760683.
8. Andersen, N. B., Malmlöf, K., Johansen, P. B., Andreassen, T. T., Ørtoft, G., & Oxlund, H. (2001). The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation in adult rats. Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society, 11(5), 266–272. https://doi.org/10.1054/ghir.2001.0239
9. Sacheck, J. M., Ohtsuka, A., McLary, S. C., & Goldberg, A. L. (2004). IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. American journal of physiology. Endocrinology and metabolism, 287(4), E591–E601. https://doi.org/10.1152/ajpendo.00073.2004
10. Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Orskov H. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999 Apr;9(2):106-13. doi: 10.1054/ghir.1999.9998. PMID: 10373343.
11. Svensson J, Lall S, Dickson SL, Bengtsson BA, Rømer J, Ahnfelt-Rønne I, Ohlsson C, Jansson JO. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. J Endocrinol. 2000 Jun;165(3):569-77. Doi: 10.1677/joe.0.1650569. PMID: 10828840.
12. Lall, S., Tung, L. Y., Ohlsson, C., Jansson, J. O., & Dickson, S. L. (2001). Growth hormone (GH)-independent stimulation of adiposity by GH secretagogues. Biochemical and biophysical research communications, 280(1), 132–138. https://doi.org/10.1006/bbrc.2000.4065
13. Laferrère, Blandine, et al. “Growth hormone-releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.” The Journal of Clinical Endocrinology and Metabolism vol. 90,2 (2005): 611-4.

CJC-1295 & Ipamorelin & GHRP-2 are research peptides that are believed to interact with different receptors on pituitary gland cells. These cells are thought to produce a wide variety of hormonal substances that consequently regulate other endocrine cells and tissues. CJC-1295 & Ipamorelin & GHRP-2, in particular, are thought to stimulate the potential of pituitary cells for synthesizing growth hormone. Here are details for each of these peptides:

• CJC-1295 belongs to a class of molecules referred to as growth hormone-releasing hormone (GHRH) agonists.^[1] It is made of the first 29 amino acids of the native GHRH hormone, representing the shortest functional sequence of GHRH. Further, CJC-1295 appears to have several modifications, including the replacement of four of the original amino acids in the GHRH 1-29 sequence, as well as the attachment of a rug affinity complex (DAC) component that may bind to plasma proteins. More specifically, the DAC component in CJC-1295 refers to the attachment of N-epsilon-3-maleimidopropionamide derivative at the C terminus. These modifications are posited to support the stability of the molecule and prolong its half-life.
• Ipamorelin, also referred to as NNC 26-0161, is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2.^[2] This molecule belongs to the family of growth hormone-releasing peptides (GHRPs), which were initially derived from the structure of endogenously occurring pentapeptides called metenkephalins. Ipamorelin appears to be highly selective towards triggering the release of growth hormone from the pituitary gland cells.
• GHRP-2 (growth hormone-releasing peptide-2) appears to belong to the GHRP class as well.^[3] It is a hexapeptide developed from the structure of met-enkephalins. Yet, GHRP-2 appears to be less selective in its actions compared to Ipamorelin.

 

Mechanisms of Action

While it is believed that all three peptides may interact with the pituitary gland cells to stimulate growth hormone release, they may do so via different mechanisms:

• Interaction with the GHRH receptors: CJC-1295 appears to function primarily via the GHRH receptors found on pituitary gland cells. These receptors normally respond to the GHRH hormone, but CJC-1295 appears to induce similar activation. When CJC-1295 binds to this receptor on pituitary cells, it may activate intracellular proteins referred to as G-proteins. This might stimulate the production of second messengers such as cyclic adenosine monophosphate (cAMP) and inositol trisphosphate (IP₃). These small molecules are believed to serve as internal signals, potentially propagating the message deeper into the cell by relaying and amplifying the signal received at the cell surface. The increase in second messengers like cAMP is believed to activate enzymes called protein kinases. Once phosphorylated, these transcription factors may enter the cell nucleus and potentially modulate the transcription of genes involved in the synthesis and secretion of growth hormone.
• Interactions with ghrelin receptors: Ipamorelin and GHRP-2 appear to interact with a different subtype of pituitary receptors, called “ghrelin receptors” or also “growth hormone secretagogue receptor 1a” (GHS-R1a). These receptors normally respond to the hunger hormone ghrelin. GHRPs like GHRP-2 and Ipamorelin are also thought to activate these receptors and are consequently also referred to as growth hormone secretagogues. Once these peptides bind to the GHS-R1a, they appear to induce conformational changes that lead to the production of transcription factors. The latter may enter the pituitary cell nucleus and modulate the transcription of genes involved in the production and release of growth hormone.

 

Scientific and Research Studies

 

CJC-1295 & Ipamorelin & GHRP-2 Blend and Growth Hormone Signaling

All three of these peptides are believed to interact with the pituitary gland cells, which may potentially stimulate the release of growth hormone. The production of growth hormone may interact with receptors on the liver, muscle cells, and other cells, potentially initiating a series of intracellular signaling events such as activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.^[4]

Following activation, STAT proteins may translocate to the nucleus and bind to specific DNA sequences referred to as response elements, which might facilitate the transcription of genes involved in the synthesis of insulin-like growth factor-1 (IGF-1). This is the main anabolic mediator of growth hormone, and CJC-1295 & Ipamorelin & GHRP-2 are expected to upregulate the synthesis of both the growth hormone and IGF-1 in experimental models. Unfortunately, no studies have investigated their potential as a blend, but several trials have experimented with each of the peptides individually and report the following observations:

• Experimental studies suggest that CJC-1295 may increase the synthesis of growth hormone by approximately 2- to 10-fold compared to placebo models.^[5] Peak levels of growth hormone are reported to occur around two hours after introducing CJC-1295, and this elevated activity might persist for up to six days. Consequently, CJC-1295 may potentially contribute to average levels of IGF-1 increasing by about 1.5- to 3-fold throughout approximately 9 to 11 days. Additionally, repeated exposure to CJC-1295 appears to maintain elevated IGF-1 levels above baseline for up to 28 days.
• In studies involving Ipamorelin, it has been observed that growth hormone levels may increase significantly, potentially reaching up to 80 milli-International Units per liter (mIU/l), which corresponds to approximately 26.6 nanograms per milliliter (ng/ml).^[6] Compared to the growth hormone levels around 1.31 mIU/l (0.4 ng/ml) with placebo, this represents what seems to be a substantial elevation in growth hormone concentration.
• Research on GHRP-2 suggests that it might stimulate growth hormone production from anterior pituitary cells up to 181 times the baseline levels.^[7] Furthermore, some studies report that IGF-1 levels may increase from an average of 100 micrograms per liter (mcg/l) at baseline to approximately 180 mcg/l following GHRP-2 exposition. Another group of researchers found that GHRP-2 appears to stimulate the pulsatile, rhythmic, and entropic secretion of growth hormone by more than threefold compared to GHRH.^[8]

 

CJC-1295 & Ipamorelin & GHRP-2 Blend and Hunger Hormone Signaling

While CJC-1295 appears to interact with the GHRH receptors, which do not affect hunger hormone signaling, Ipamorelin & GHRP-2 interact with the GHSR1a receptors, which are also referred to as the ghrelin receptors as the hunger hormone ghrelin activates them. Activation of GHSR1a receptors may promote the production of hunger hormone-stimulating neuropeptides, such as neuropeptide Y (NPY) and agouti-related peptide (AgRP), while potentially suppressing the release of alpha-melanocyte-stimulating hormone (α-MSH), an appetite-suppressing hormone.

Some studies have suggested that laboratory models exposed to Ipamorelin may experience a notable increase in hunger hormone signaling. This may lead to an increase in the size and weight of research models by approximately 15%, possibly due to a rise in adipose tissue relative to total mass.^[9] Additionally, research indicates that models exposed to GHRP-2 may consume approximately 36% more food than control models, suggesting an increase in food intake relative to mass. Specifically, the energy intake per kilogram of mass in the GHRP-2 group was observed to be 136.0±13.0 kilojoules per kilogram, compared to 101.3±10.5 kilojoules per kilogram in the control group.^[10]

 

CJC-1295 & Ipamorelin & GHRP-2 Blend in Bone Tissues

Some research suggests that Ipamorelin might support bone formation and possibly increase overall bone mass.^[11,12] This hypothesis arises from observations implying that Ipamorelin might be associated with an apparent rise in bone mineral content (BMC), which refers to the total amount of minerals in bone tissue. In a particular study involving murine models, scientists examined the potential actions of Ipamorelin on bone mineral content. Researchers have proposed that Ipamorelin may lead to increases in the size, weight, and bone mineral content of experimental animals.

These changes might be measured using dual-energy X-ray absorptiometry (DXA). This non-invasive imaging technique assesses bone density by gauging how bones and soft tissues absorb X-rays. The researchers also commented, “that the increases in cortical and total BMC were due to an increased growth of the bones with increased bone dimensions, whereas the volumetric BMD was unchanged.” Therefore, Ipamorelin appears to mediate this potential by apparently upregulating anabolic growth signals like growth hormone and IGF-1. The addition of CJC-1295 and GHRP-2 may further upregulate this potential, although research is lacking.

 

CJC-1295 & Ipamorelin & GHRP-2 Blend in Muscle Cell Hypertrophy

The potential upregulation of growth hormone and IGF-1 levels by peptides like CJC-1295 & Ipamorelin & GHRP-2 is also expected to lead to increased anabolic signaling with muscular tissue, which is associated with muscle cell hypertrophy (increase in cell size). For example, preliminary research with CJC-1295 analogs suggests that the peptide may induce a notable increase in muscle tissue hypertrophy, leading to an average net gain of lean mass of about 2.77 pounds within 16 weeks.^[13]

Researchers have also posited that “GHRP-2 enhanced muscle protein deposition mainly by

up-regulating the protein synthesis pathways” when conducting research in yaks. The study suggested that GHRP-2 may help to overcome endogenous growth limitations that occur in yaks because of food deprivation, adverse environmental conditions, and disease. Furthermore, GHRP-2 may have indicated potential contributions to reduction in atrophy of muscular tissue through repression of muscle cell-specific enzymes called E3 ubiquitin ligases—such as atrogin-1 and muscle ring finger protein-1 (MuRF1), which are believed to upregulate muscle cell degradation pathways. Specifically, these enzymes are thought to tag proteins for degradation via the ubiquitin-proteasome pathway, a cellular system responsible for breaking down proteins.

It is also theoretically possible that Ipamorelin may also help reduce the loss of muscle cells in catabolic experimental models. This potential might occur by increasing the IGF-1 within muscular tissue. For instance, studies suggest that Ipamorelin may decrease muscular tissue loss in research models exposed to corticosteroids, which are believed to induce the wasting of muscular tissues.^[15] The mechanisms underlying this potential action might involve the suppression of atrogin-1 and MuRF1, mediated by IGF-1. By possibly downregulating these ligases, IGF-1 may reduce muscle cell protein degradation and assist in preserving muscle cells.^[16]

 

CJC-1295 & Ipamorelin & GHRP-2 Blend Synergy

Given that CJC-1295 may operate through a different biological pathway than Ipamorelin and GHRP-2, which are synthetic growth hormone secretagogues, some researchers hypothesize that combining these compounds may produce a synergistic action on somatotroph cells and induce an even greater growth hormone synthesis. For example, some scientists point to studies that have investigated potential synergism between similar compounds.

For example, one study examined a CJC-1295 analog and GHRP-2, reporting that each peptide individually may have led to a 20-fold and 47-fold increase, respectively, in the pulsatile secretion of growth hormone from anterior pituitary somatotroph cells.^[17] However, when both compounds were applied simultaneously, the increase in growth hormone secretion may have reached 54-fold, suggesting a possible synergistic interaction. More research is needed to investigate the potential synergy between CJC-1295 and GHRP-2 and how it may be affected by the addition of Ipamorelin.

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