Comprehensive Research on ACE-031 Peptide Across Metabolism, Cancer, and Muscle

Comprehensive Research on ACE-031 Peptide Across Metabolism, Cancer, and Muscle

ACE-031 peptide, referred to as ActRIIB-IgG1 peptide, is identified as a myostatin inhibitor. Structurally, it constitutes a fusion compound merging activin receptor type IIB (ACV2RB) with recombinant immunoglobulin IgG1 FC, an antibody variant.[1]

ACE-031 - Myostatin inhibitory peptide 7

Research[2] suggests its solubility and potential to impede circulating myostatin, ostensibly averting the inhibitory action that native ACV2RB receptors are considered to have, fostering muscle growth. Myostatin, or growth and differentiation factor 8 (GDF8), is subject to inhibition by certain compounds termed inhibitors, targeting its action as a putative negative regulator of muscle growth primarily localized in skeletal muscle tissues.

Notably, myostatin’s influence appears absent in cardiac or smooth muscle tissues. Its discovery dates back to 1997, rooted in its observed inhibitory role in muscle growth, which was elucidated through murine studies. Myostatin purportedly restrains murine satellite cell activation, representing partially committed stem cells within muscle tissue. Experimental models suggest myostatin overexpression may lead to diminished muscle mass.

Myostatin is presumed to bind with a high affinity to ActR2B receptors, initiating a signaling cascade involving Smad2/3 pivotal for muscle regulation. Other ligands within the transforming growth factor-beta (TGF-β) superfamily, such as various GDFs and activins, may bind ActR2B and regulate muscle growth. ACE-031’s mechanism appears to involve binding with circulating members of the TGF-β superfamily, particularly myostatin, potentially leaving ACV2RB receptors uninhibited[3], thereby triggering muscle hypertrophy and augmenting skeletal muscle tissue size. Additionally, ACE-031 may exert positive effects on metabolism, fat storage, and bone density.


ACE-031 Peptide and Lipid Metabolism

Investigations[4] into ACE-031’s impact on fat metabolism within the context of obesity research have unveiled intriguing insights. Recent studies have hinted at a potential correlation between myostatin expression and obesity, suggesting its involvement in metabolic pathways. Notably, in murine obesity models, elevated levels of myostatin and its receptor ActR2b have been observed compared to lean counterparts. Experimental manipulations inducing myostatin overexpression in these models have suggested a concurrent decline in muscle and myocardial mass alongside an increase in adipose tissue, implying a possible role of myostatin in promoting adiposity and reducing muscle mass.

Conversely, myostatin depletion in select murine models presents a possible research path for mitigating age-related adipose tissue accumulation and partially alleviating obesity-related traits. Furthermore, observations in mice subjected to high-calorie diets suggest that myostatin deficiency may lead to “enhanced peripheral tissue fatty acid oxidation and increased thermogenesis, culminating in increased fat utilisation and reduced adipose tissue mass.”

In light of these findings, researchers are exploring the potential of ACE-031 in obesity-related complications in murine models. Preliminary findings[5] suggest that ACE-031 may have promise in preventing and mitigating obesity-associated phenotypes.


Research in Muscle Tissue Hypertrophy

In a rigorously designed experimental framework structured as a double-blind, placebo-controlled research study,[6] the potential of ACE-031 in muscle tissue was explored alongside a comprehensive pharmacokinetic analysis. According to the pharmacokinetic analysis report, ACE-031 exhibited a half-life estimated to range between 10 to 15 days. The findings of this study suggested a potential augmentation in muscle mass following exposure to ACE-031. This inference was drawn from meticulous assessments of muscle tissue alterations, quantified through precise measurement techniques, including dual-energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI) conducted 29 days post-peptide exposure.

The results indicated a possible surge in muscle mass, seen in a 3.3% escalation in total lean mass and a 5.1% increase in quadriceps femoris muscle volume. Furthermore, notable shifts in serum biomarkers were observed, suggesting potential bone and fat metabolism enhancements. These percentages underscore profound alterations in muscle tissue, indicative of ACE-031’s potential to stimulate hypertrophy.


ACE-031 Peptide and Muscle Contractility

Ongoing research[7] has proposed that the peptide’s action may extend beyond myostatin inhibition. ACE-031 may enhance muscle contractile force by potentially mitigating oxidative stress within muscle tissues, conserving energy, and fostering oxidative respiration within muscles. These hypotheses stem from observations conducted in murine models, with assessments facilitated through magnetic resonance imaging (MRI) and dynamic [31P]-magnetic resonance spectroscopy ([31P]-MRS).

Specifically, exposure to ACE-031 appeared to yield a marked increase in muscle volume, with no discernible alteration in the distribution of muscle fiber types. This suggests a potential role for the peptide in promoting muscle growth. Furthermore, murine models exhibited a notable elevation in basal oxygen consumption and energy expenditure, indicative of heightened metabolic activity. During standardized fatiguing exercises, animal models exposed to ACE-031 reportedly exhibited enhanced muscle performance in a significantly higher maximum and total absolute contractile forces compared to the control group.

However, it is pertinent to note that while ACE-031 appeared to boost muscle contractile forces, it did not seem to affect the specific force-generating capacity or fatigue resistance. Moreover, metabolic fluxes, adenosine triphosphate (ATP) homeostasis, and contractile efficiency during exercise appeared to have remained largely unaffected. Intriguingly, ACE-031 seemed to diminish the intrinsic mitochondrial capacity for ATP production, hinting at potential alterations in energy generation pathways within muscle cells. However, the precise implications of this finding warrant further investigation.


Studies on Energy Metabolism

Studies have indicated that inhibiting endogenous ACE-031 proteins might not effectively lower serum lactate levels, potentially impeding the occurrence of metabolic damage to muscles and the vascularization of muscle tissue. However, supplementation with ACE-031 may potentially mitigate such impacts. ACE-031 supplementation is speculated to foster muscle cell growth by thwarting myostatin-mediated wasting. Moreover, it may postpone the onset of fatigue and oxidative damage by enhancing muscle tissue oxygenation.


ACE-031 Peptide and Bone Density

A study[8] delved into the potential action of ACE-031 on bone tissue in murine models of Duchenne Muscular Dystrophy (DMD), or muscle degeneration and heightened fracture susceptibility. The models were categorized into groups based on their activity level (running or sedentary) and further subdivided into active or placebo cohorts.

The research indicated that ACE-031 led to noticeable increases in body and muscle weights in sedentary and exercising murine models. Notably, researchers reported that femoral micro-CT analysis appeared to exhibit a substantial bone volume and trabecular number enhancement within the ACE-031 groups. While running also seemed to enhance these bone parameters in the control group, it did not notably improve trabecular bone structure or volumetric bone mineral density.

Furthermore, ACE-031 was implicated in augmenting bone mass in vertebral tissue. According to research, “the number of osteoclasts was decreased in histological analysis and the expression of several osteoblast marker genes was increased in ActRIIB-Fc treated mice, suggesting decreased bone resorption and increased bone formation in these mice.”


ACE-031 Peptide and Cancer

Molecular pathways contributing to muscle loss, often attributed to apoptosis or necrosis, are frequently observed in cancer research. The principal instigator is the metabolic strain on muscles induced by alterations in aerobic respiration status. Concurrently, an elevation in intracellular free radical levels appears to indirectly exacerbate muscle damage. Intervention with ACE-031 appears to activate the ERK1/2 pathway, thereby potentially mitigating muscle fiber atrophy stemming from apoptosis. Moreover, research indicates possible enhancements in energy utilization efficiency and mitochondrial metabolism following ACE-031 exposure, concomitant with a reduction in free radical concentration.

Furthermore, certain cancers may produce myostatin, exacerbating muscle wasting. These malignancies are often characterized by deactivated activin receptors, mitochondrial loss, and subsequently, diminished ATP levels. Studies suggest a reversal of these detrimental effects upon exposure to ACE-031. Beyond mitigating myostatin-induced muscle wasting, ACE-031 inhibition may potentially exert various ancillary downstream impacts, including enhanced insulin sensitivity, reduced fat deposition, attenuated inflammation, and improved bone metabolism and strength. Research is still ongoing.

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.



  1. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 118732224, Myostatin inhibitory peptide 7.
  2. McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997 May 1; 387(6628):83-90.
  3. Ozawa T, Morikawa M, Morishita Y, Ogikubo K, Itoh F, Koinuma D, Nygren PÅ, Miyazono K. Systemic administration of monovalent follistatin-like 3-Fc-fusion protein increases muscle mass in mice. iScience. 2021 May 14;24(5):102488. doi: 10.1016/j.isci.2021.102488. PMID: 34113826; PMCID: PMC8170004.
  4. Yang M, Liu C, Jiang N, Liu Y, Luo S, Li C, Zhao H, Han Y, Chen W, Li L, Xiao L, Sun L. Myostatin: a potential therapeutic target for metabolic syndrome. Front Endocrinol (Lausanne). 2023 May 23;14:1181913. doi: 10.3389/fendo.2023.1181913. PMID: 37288303; PMCID: PMC10242177.
  5. Zhang C, McFarlane C, Lokireddy S, Masuda S, Ge X, Gluckman PD, Sharma M, Kambadur R. Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice. Diabetologia. 2012 Jan;55(1):183-93. doi: 10.1007/s00125-011-2304-4. Epub 2011 Sep 17. Erratum in: Diabetologia. 2015 Mar;58(3):643. PMID: 21927895.
  6. Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013 Mar;47(3):416-23.
  7. Béchir N, Pecchi E, Vilmen C, Le Fur Y, Amthor H, Bernard M, Bendahan D, Giannesini B. ActRIIB blockade increases force-generating capacity and preserves energy supply in exercising mdx mouse muscle in vivo. FASEB J. 2016 Oct;30(10):3551-3562.
  8. Puolakkainen, Tero et al. “Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy.” BMC musculoskeletal disorders vol. 18,1 20. 19 Jan. 2017.
  9. Image 1 Source:
AICAR Peptide: Insulin Sensitivity, Apoptosis, and Endurance

AICAR Peptide: Insulin Sensitivity, Apoptosis, and Endurance

In the realm of cellular energetics and metabolic regulation, the peptide AICAR has emerged as a pivotal research compound as it appears to offer compelling prospects for research exploration.

Analogous to adenosine monophosphate (AMP), a fundamental nucleotide pivotal in cellular energy metabolism, AICAR (short for 5-aminoimidazole-4-carboxamide ribonucleotide)[1] has garnered attention for its potential in various realms of scientific inquiry.

A significant aspect of AICAR’s potential lies in its ability to potentially reduce reperfusion injury following tissue ischemia and to potentially improve metabolic disorders. The key to how it works seems to lie in its activation of AMP-activated protein kinase (AMPK), an enzyme that plays a vital role in many metabolic processes inside cells. AMPK’s job involves bringing the cell’s energy back into balance by controlling processes that either use up energy (like making proteins and fats) or produce energy (like breaking down glucose and fats).[1] By slowing down energy-consuming processes and speeding up energy-producing ones, AMPK is considered to help cells generate more ATP, the energy currency of cells.

Moreover, the influence of AMPK extends beyond mere energy regulation, encompassing pivotal cellular processes including autophagy, mitochondrial biogenesis, and inflammatory modulation. Due to its potential to activate AMPK, AICAR peptide offers possible pathways to increase the uptake of glucose in skeletal muscle, improve sensitivity to insulin, and enhance tolerance to glucose. Additionally, scientists are considering its anti-inflammatory potential and the possibility of improving physical performance in certain experimental conditions. As such, the interplay between AICAR peptide and AMPK unveils several possibilities, requiring further investigation into its multifaceted roles.


AICAR Peptide and Organ Protection

Researchers suggest peptide may exhibit promise in conferring organ-protective impacts, particularly concerning ischemia and reperfusion injury. Initial investigations suggest that AICAR may attenuate myocardial infarction size and enhance cardiac function in an animal model subjected to myocardial ischemia-reperfusion injury.[2]

Notably, a meta-analysis encompassing data from five randomized, placebo-controlled, double-blind studies[3] further explored AICAR’s potential in cardiovascular contexts. The analysis indicated that peptide exposure may have been associated with reductions in myocardial tissue infarction size and cardiac cell death, potentially leading to improved overall outcomes. This protective potential of peptide is suggested by researchers to stem from its influence on cellular metabolism, possibly rendering cells more resilient to hypoxic conditions by upregulating energy availability, notably myocardial glucose. Experimental data from murine models suggests that AICAR, through AMPK activation, “may participate in the control of glycogen metabolism.” Furthermore, AICAR exposure was correlated with elevated levels of 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranotide (ZMP), its active intracellular form. Although AICAR did not appear to notably impact the activity of glycogen synthase (GS) or glycogen phosphorylase (GP) in tissue homogenates, it seemingly facilitated glycogenolysis through allosteric activation of GP, potentially providing an alternative energy substrate during cellular stress.[4]

Beyond its cardioprotective potential, research suggests that peptide “appears to protect the liver from fatty changes associated with chronic alcohol [exposure]” as observed in experimental murine models. Chronic ethanol exposure typically induces histological and biochemical changes indicative of fatty liver. However, AICAR intervention appeared to have attenuated these alterations, potentially by downregulating hepatic sterol regulatory element-binding protein 1c (SREBP-1c) expression and reducing fatty acid synthase (FAS) enzyme activity. SREBP-1c, a key regulator of lipid metabolism primarily in hepatic tissues, is considered by scientists to modulate the expression of genes involved in cholesterol, fatty acid, and triglyceride synthesis. Consequently, the observed decrease in SREBP-1c levels following peptide exposure likely contributes to diminished fatty acid synthesis. Meanwhile, FAS, a pivotal enzyme in fatty acid biosynthesis, appears to be regulated by SREBP-1c, further implicating AICAR in attenuating hepatic lipid accumulation.[5]


AICAR and Physical Activity

AICAR peptide has garnered considerable attention by researchers in studies in the realm of physical endurance, with researchers hypothesizing its potential to activate key metabolic pathways to improve and increase activity. Specifically, studies suggest that AICAR may activate enzymes such as AMPK, glycogen phosphorylase, and fructose-1,6-bisphosphatase, leading to potential enhancements in oxidative metabolism and the creation of new mitochondria, a process known as mitochondrial biogenesis.[6] The augmentation of mitochondrial quantity and function is suggested to confer benefits to muscle endurance. For instance, experimental data indicates that AICAR exposure in sedentary murine models appeared to have resulted in a substantial improvement in running endurance, potentially attributable to the induction of metabolic genes. These findings imply that peptides may modulate the AMPK-PPARδ pathway to facilitate training adaptations or augment endurance capacity without the need for physical exercise.[7]

PPARδ, short for Peroxisome Proliferator-Activated Receptor Delta, represents a class of nuclear receptors implicated in the regulation of genes associated with energy metabolism. It is hypothesized that PPARδ may influence processes such as lipid oxidation and mitochondrial biogenesis. The AMPK-PPARδ pathway is proposed as a conduit between the energy-sensing function of AMPK and the gene regulatory role of PPARδ. Activation of this pathway potentially induces adaptations in muscle cells akin to those induced by prolonged physical activity, including heightened mitochondrial content and a shift in muscle fiber composition towards endurance-oriented fibers, thereby potentially augmenting endurance capacity.

Further experiments in murine models have provided additional insights into the potential of peptide in augmenting endurance.[8] Notably, the introduction of an AMP-activated protein kinase agonist appeared to have resulted in increased endurance compared to controls. Additionally, in a murine model of Duchenne muscular dystrophy, AICAR appeared to have the potential to enhance the effects of physical activity and muscle function, possibly through the stimulation of autophagy.

Moreover, investigations into the vascular effects of peptide have revealed intriguing findings. Infusion of AICA-riboside, a precursor of AICAR, was associated with correlated increases in forearm blood flow, potentially mediated by nitric oxide. This suggests a potential dual role for AICAR in improving muscle blood flow and acting as a nitric oxide booster, both of which are critical factors in prolonged physical activity.[9]


AICAR Peptide and Insulin Sensitivity

Research suggests that AICAR may enhance the insulin sensitivity of various tissues by activating AMPK within cells, thereby facilitating glucose uptake. In an experimental model focusing on equine skeletal muscle, AICAR exposure appeared to lead to a decrease in glucose levels and an increase in insulin concentration, while lactate concentration remained unaffected. Notably, AICAR potentially augmented the ratio of phosphorylated to total AMPK in skeletal muscle and may have upregulated GLUT8 protein expression. The observed elevation in GLUT8 protein expression could potentially enhance glucose transport into cells, consequently improving insulin sensitivity.

Moreover, a study[10] investigating AICAR’s impact on muscle glucose uptake alongside physical activity revealed a potential increase in glucose uptake in muscle tissue. This effect might extend beyond muscle tissue, potentially enhancing peripheral and overall insulin sensitivity. Researchers also proposed that peptide might elevate the phosphorylation of extracellular signal-regulated kinase 1/2, enzymes crucial in the MAP kinase/ERK pathway, which regulates cellular processes like division, differentiation, and stress response.

Furthermore, investigations suggest that AICAR may potentially decrease hepatic glucose output, lower glucose concentrations, promote hepatic fatty acid oxidation, and inhibit lipolysis, consequently reducing plasma-free fatty acid availability.[11] Although no increase in AMPK phosphorylation was reported in skeletal muscle, a significant rise in acetyl-CoA carboxylase phosphorylation was observed. This enzyme is considered to play a pivotal role in fatty acid metabolism, catalyzing the conversion of acetyl-CoA to malonyl-CoA, a critical step in fatty acid synthesis. The apparent inactivation of acetyl-CoA carboxylase is speculated to stimulate “hepatic fatty acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA concentration.”


AICAR Peptide and Cellular Apoptosis

Data from research studies suggests that peptide may instigate programmed cell death, known as apoptosis, in test models of B-cell chronic lymphocytic leukemia (B-CLL).

Specifically, one study[12] posits that this phenomenon might entail the activation of specific enzymes involved in apoptosis, including caspase-3, -8, and -9, alongside the release of cytochrome C. Furthermore, the incubation of B-CLL cells with AICAR appears to stimulate the phosphorylation of AMP-activated protein kinase (AMPK), indicating the potential of peptide in activating this protein. Investigation into the cellular mechanisms underlying AICAR-induced apoptosis explored the necessity of AICAR’s entry into the cell and its subsequent conversion to AICA ribotide (ZMP). This inquiry employed various inhibitors, such as Nitrobenzylthioinosine (NBTI), 5-iodotubercidin, and adenosine, which were hypothesized to impede AICAR-induced apoptosis and AMPK phosphorylation. Interestingly, inhibitors targeting protein kinase A and mitogen-activated protein kinases did not seem to hinder AICAR-induced apoptosis in B-CLL cells.

Moreover, the study observed that peptide did not appear to have significantly impacted the levels or phosphorylation of p53, suggesting a mechanism of apoptosis independent of p53 activation in B-CLL cells. A comparative analysis of the sensitivity of normal B lymphocytes, T cells, and B-CLL cells to AICAR-induced apoptosis appeared to reveal similar susceptibility between normal B lymphocytes and B-CLL cells, with T cells from B-CLL subjects displaying only marginal sensitivity. Notably, the phosphorylation of AMPK was not observed in T cells exposed to AICAR. Furthermore, upon AICAR exposure, B-CLL cells appeared to have exhibited higher intracellular levels of ZMP compared to T cells, implying that the accumulation of ZMP may play a pivotal role in activating AMPK and prompting apoptosis in these cells.

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.



  1. National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 65110, AICA ribonucleotide
  2. Cieslik, K. A., Taffet, G. E., Crawford, J. R., Trial, J., Mejia Osuna, P., & Entman, M. L. (2013). AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction. Journal of molecular and cellular cardiology, 63, 26–36.
  3. Mangano D. T. (1997). Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. The Multicenter Study of Perioperative Ischemia (McSPI) Research Group. JAMA, 277(4), 325–332.
  4. Longnus, S. L., Wambolt, R. B., Parsons, H. L., Brownsey, R. W., & Allard, M. F. (2003). 5-Aminoimidazole-4-carboxamide 1-beta -D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms. American journal of physiology. Regulatory, integrative and comparative physiology, 284(4), R936–R944
  5. Tomita, K., Tamiya, G., Ando, S., Kitamura, N., Koizumi, H., Kato, S., Horie, Y., Kaneko, T., Azuma, T., Nagata, H., Ishii, H., & Hibi, T. (2005). AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats. Alcoholism, clinical and experimental research, 29(12 Suppl), 240S–5S.
  6. Hardie DG. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev. 2011 Sep 15;25(18):1895-908. doi: 10.1101/gad.17420111. PMID: 21937710; PMCID: PMC3185962.
  7. Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y. X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., Kang, H., Shaw, R. J., & Evans, R. M. (2008). AMPK and PPARdelta agonists are exercise mimetics. Cell, 134(3), 405–415.
  8. Goodyear, L. J. (2008). The exercise pill—too good to be true? New England Journal of Medicine, 359(17), 1842-1844.
  9. Bosselaar, M., Boon, H., van Loon, L. J., van den Broek, P. H., Smits, P., & Tack, C. J. (2009). Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in vivo in human skeletal muscle. American journal of physiology. Endocrinology and metabolism, 297(3), E759–E766.
  10. Cuthbertson, D. J., Babraj, J. A., Mustard, K. J., Towler, M. C., Green, K. A., Wackerhage, H., Leese, G. P., Baar, K., Thomason-Hughes, M., Sutherland, C., Hardie, D. G., & Rennie, M. J. (2007). 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes, 56(8), 2078–2084.
  11. Boon, H., Bosselaar, M., Praet, S. F., Blaak, E. E., Saris, W. H., Wagenmakers, A. J., McGee, S. L., Tack, C. J., Smits, P., Hargreaves, M., & van Loon, L. J. (2008). Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. Diabetologia, 51(10), 1893–1900.
  12. Campàs, C., Lopez, J. M., Santidrián, A. F., Barragán, M., Bellosillo, B., Colomer, D., & Gil, J. (2003). Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood, 101(9), 3674–3680.
GHRP-2 Peptide – Research in Growth Hormone Deficiency Diagnosis and Hormonal Modulation

GHRP-2 Peptide – Research in Growth Hormone Deficiency Diagnosis and Hormonal Modulation

Growth Hormone Releasing Peptide-2 (GHRP-2), also known as pralmorelin, stands as a synthetic peptide reportedly designed to mimic the actions of ghrelin,[1] an endogenous peptide considered to be crucial in various physiological processes. Ghrelin, initially discovered in stomach tissues and comprised of 28 amino acids, is considered by scientists to play pivotal roles in regulating food intake, growth hormone release, and wound healing.[2]

GHRP-2, the pioneer among growth hormone secretagogues, has been suggested by researchers to operate by binding to the ghrelin/growth hormone secretagogues receptor, thereby triggering the secretion of growth hormone.

Pralmorelin (GHRP-2)

This synthetic peptide has garnered significant attention among researchers in diverse domains of study. Researchers suggest that GHRP-2 may potentially serve as a tool for evaluating growth hormone deficiency and secondary adrenal failure. Concurrently, ongoing research endeavors delve into its diverse potential effects, theories of which encompass appetite modulation, muscle cell proliferation, immune system modulation, and regulation of sleep cycles.

Additionally, studies conducted in bovine models have indicated potential multifaceted impacts of GHRP-2, suggesting its involvement in stimulating growth hormone secretion via interactions with growth hormone release factor receptors, calcium channels, and signaling pathways like the cAMP pathway and protein kinase C activation.[3]

These mechanisms are speculated to collectively contribute to the elevation of growth hormone levels, implicating GHRP-2 as a promising agent in various physiological contexts.


GHRP-2 Peptide and Growth Hormone (GH) Deficiency

Existing conventional procedures to identify growth hormone (GH) deficiency may involve testing insulin tolerance; however, they may potentiate adverse effects and contradictions. To address these limitations, one investigation[4] sought to evaluate the utility of Growth Hormone Releasing Peptide-2 (GHRP-2) as an alternative diagnostic for GH deficiency in laboratory settings.

The researchers conducted initial testing of the research model via ITT. Blood samples were collected and analyzed after a 2-hour interval. Results indicated a consistent peak in GH levels one hour post-GHRP-2 exposure. However, a marginal decrease in efficacy was observed in certain models of obesity or advanced age. The study results suggest the diagnostic potential of GHRP-2 in severe GH deficiency research, acknowledging minor influences from age and adiposity levels.

In a separate study[3], the diagnostic efficacy of GHRP-2 compared to conventional compounds often studied in conjunction with growth hormone deficiency (GHD) was explored. Research models of GHD, having undergone exposure with at least one conventional medication, were subjects of this study. The researchers suggested that additional exposure to GHRP-2 may have acted as a reliable predictor of the pituitary gland’s capacity to release GH, a feature not reported with the conventional compounds in isolation.


GHRP-2 Peptide and Caloric Intake

In a controlled experimental setting,[6] researchers attempted to investigate the impact of Growth Hormone Releasing Peptide-2 (GHRP-2) on food consumption. An experimental research model group was exposed to GHRP-2, compared to a separate control group exposed to saline over a 4.5-hour period. Subsequently, researchers monitored food intake. Results indicated a notable increase in food consumption among the GHRP-2 group, exhibiting a mean increase of approximately 36% compared to the saline group.

These findings suggest the possible action of GHRP-2 in stimulating appetite, as indicated by the substantial increase in food consumption observed in the experimental group. Moreover, the concurrent rise in GH levels further underlies the hypothetical physiological action of GHRP-2 in regulating appetite and metabolism.


General Action

Numerous investigations[5] conducted on animals elucidate the potential impacts of GHRP-2 peptide. In both rabbits and guinea pigs, the exposure of GHRP-2 appears to exhibit no discernible effects on the central nervous system. Notably, apart from a modest increase in the motility of the isolated rabbit ileum and enhanced contraction of the isolated guinea pig ileum at higher GHRP-2 concentrations, no other significant effects were observed. Moreover, GHRP-2 exposure reportedly may not elicit alterations in the respiratory, digestive, renal, and circulatory systems. As per the researchers, the peptide “has no serious general [effects] at [concentration] levels showing GH-releasing activity in the experimental animals,” and the peptide is speculated to support the diagnosis of “serious GH deficiency and short stature.”[5]


Combination Studies with TRH and GnRH

A research study[7] aimed to assess the effects of GHRP-2, Thyrotropin Releasing Hormone (TRH), and Gonadotropin Releasing Hormone (GnRH) alone and in various combinations on research models of prolonged hyposomatotropism, hypogonadism, or hypothyroid complications.

Over the course of five days, the researchers evaluated the action of three compounds: placebo, GHRP-2 alone every hour, GHRP-2 and TRH every hour, and GHRP-2, TRH, and GnRH every 90 minutes. Serum samples were collected on the first and last nights of the study period for analysis.

Analysis of the results suggests that the combination of GHRP-2, GnRH, and TRH elicited the most pronounced activation of growth hormone, thyroid stimulating hormone, and luteinizing hormone axes, accompanied by potential metabolic effects. Conversely, the effects observed with GHRP-2 alone were reported to be minimal, and even the combination of GHRP-2 and TRH appeared to only partially induce similar effects compared to the triple combination regimen.

These findings underscore the potential synergistic action of GHRP-2 with GnRH and TRH in eliciting robust hormonal responses in experimental settings.


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.



  1. Garcia JM, Merriam GR, Kargi AY. Growth Hormone in Aging. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext. South Dartmouth (MA):
  2. GHRP 2, GPA 748, Growth Hormone-Releasing Peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102 LN.
  3. Asad Rahim, Stephen M. Shalet, in Growth Hormone Secretagogues, 1999. Does desensitization to growth hormone secretagogues occur?
  4. Roh SG, He ML, Matsunaga N, Hidaka S, Hidari H. Mechanisms of action of growth hormone-releasing peptide-2 in bovine pituitary cells. J Anim Sci. 1997 Oct;75(10):2744-8. doi: 10.2527/1997.75102744x. PMID: 9331879.
  5. Furuta S, Shimada O, Doi N, Ukai K, Nakagawa T, Watanabe J, Imaizumi M. General pharmacology of KP-102 (GHRP-2), a potent growth hormone-releasing peptide. Arzneimittelforschung. 2004;54(12):868-80. doi: 10.1055/s-0031-1297042. PMID: 15646371.
  6. 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.
  7. Van den Berghe G, Baxter RC, Weekers F, Wouters P, Bowers CY, Iranmanesh A, Veldhuis JD, Bouillon R. The combined administration of GH-releasing peptide-2 (GHRP-2), TRH and GnRH to men with prolonged critical illness evokes superior endocrine and metabolic effects compared to treatment with GHRP-2 alone. Clin Endocrinol (Oxf). 2002 May;56(5):655-69. doi: 10.1046/j.1365-2265.2002.01255.x. PMID: 12030918.
  8. Image source: National Center for Biotechnology Information (2024). PubChem Compound Summary for CID 6918245, Pralmorelin.
Nonapeptide-1: Research on Skin Pigmentation

Nonapeptide-1: Research on Skin Pigmentation

Nonapeptide-1 peptide initially derived from the yeast Streptomyces clavifer, is currently synthesized using recombinant genetic technology. This peptide since appears to have evolved into a potent inhibitor of melanin formation, as suggested in laboratory studies involving yeast and melanoma (skin cancer) cells.[1]

Comprising the amino acids arginine, lysine, methionine, phenylalanine, proline, tryptophan, and valine, Nonapeptide-1 first emerged in the 1990s as a subject of scientific inquiry, primarily for its proposed capacity to impede melanin synthesis. Melanin is a primary pigment in mammals governing skin, fur, hair, and ocular coloration. Despite initial interest, the understanding of Nonapeptide-1 remains rudimentary, with many aspects of its mechanisms and potential yet to be elucidated.

Research on Nonapeptide-1 has concentrated on its putative role in melanin production inhibition by disrupting the signaling cascade intrinsic to melanogenesis. Specifically, investigations suggest that Nonapeptide-1 may interfere with melanocortin-1 receptor function, potentially impeding the action of melanocyte-stimulating hormones and hindering the activation of tyrosinase, an essential enzyme in melanin synthesis. Preliminary animal studies indicate a possible attenuation of hyperpigmentation and modulation of skin tone with Nonapeptide-1 exposure. However, comprehensive investigations are imperative to grasp the peptide’s complete potential.


Mechanism of Action

Nonapeptide-1, at a technical level, appears to exhibit capacity as a melanin synthesis inhibitor, reportedly achieved through interference with the action of tyrosinase. Tyrosinase, the principal enzyme governing melanin synthesis within specialized cells termed melanocytes, is considered crucial for pigment production. Nonapeptide-1’s apparent interference with tyrosinase function appears to impede melanocyte pigment production.[2,3]

Consequently, through this mechanism, researchers suggest that Nonapeptide-1 may demonstrate potential in animal studies to diminish skin pigmentation, thereby ameliorating hyperpigmented areas caused by sun exposure and certain pathologies.

Emerging scientific data also suggests that Nonapeptide-1 may exert its effects by modulating the activity of melanocyte-stimulating hormone (MSH). MSH levels elevate during specific physiological states such as pregnancy, certain disorders (e.g., diabetes, Addison’s disease), and excessive sun exposure. MSH, derived from adrenocorticotropic hormone, is considered to play a pivotal role in skin pigmentation regulation. Synthetic analogs of MSH, like melanotan II, has been proposed to mimic its effects and induce skin darkening. Intriguingly, the responsiveness to MSH appears to vary; with some research models exhibiting apparent diminished responsiveness due to genetic variations in MSH receptors, resulting in inadequate MSH-mediated effects on melanocytes.


Nonapeptide-1 and Dermal Pigmentation

Research into the potential effects of Nonapeptide-1 has been conducted in both clinical and laboratory environments. In a particular in vitro investigation, keratinocyte cell line (HaCaT) cells and epidermal melanocytes (HEM) were subjected to UVA exposure and then introduced with varying concentrations of the acetate salt of Nonapeptide-1.[4]

Examinations of cell viability, melanin content, and tyrosinase activity were carried out. The findings suggested that Nonapeptide-1 exhibited the capability to downregulate melanocortin 1 receptor expression without impacting α-MSH levels. Moreover, it appeared to significantly diminish the expression of tyrosinase, TRP1 (tyrosinase-related protein-1), TRP2 (tyrosinase-related protein-2), and MITF (microphthalmia-associated transcription factor), both in the presence and absence of concurrent UVA radiation. Additionally, the researchers proposed that cells exposed to Nonapeptide-1 displayed potential to resist melanin production.

Recent investigations into Nonapeptide-1 hypothesize a noticeable skin lightening effect, estimated to be at least 33%, with indications of continued lightening over time.[5]

The sole clinical trial on this subject was a prospective double-blinded parallel-group randomized controlled pilot study spanning eight months and comprising three phases.[6] Researchers reported an observable amelioration in severity scores of melasma and mean melanin index. As per the researchers, “The melasma area and severity index score showed a consistent reduction in the case group, whereas it increased in the control group from baseline.”


Nonapeptide-1 Future Research

In addition to melanocytes, Nonapeptide-1 may potentially target melanocortin-1 receptors expressed in various cell types, including nerve and immune cells. Specifically, these receptors have been identified in the periaqueductal gray matter, a region pivotal in nociception.[7]

Experiments conducted on mice with heightened expression of an endogenous melanocortin 1 receptor antagonist, in comparison to control mice, shed light on their responses to both painful and non-painful stimuli, as well as their reactions to inflammatory and neuropathic pain. Furthermore, their aversion to capsaicin, which activates the TRPV1 noxious heat receptor, was assessed using a paired preference paradigm.

Mice exhibiting elevated levels of the melanocortin 1 receptor antagonist showcased a diminished inflammatory pain response, slower onset of inflammation-induced hypersensitivity and allodynia, and reduced aversion to moderate capsaicin concentrations. Notably, these effects were discernible solely in female mice, with no “effect of mutant genotype on neuropathic pain” on mice of either sex.[8]

Moreover, investigations suggest a potential involvement of melanocortin 1 receptors in the proliferation and survival of melanoma tumor cells.[9] Melanoma may exhibit alterations in risk associated with mutations in the melanocortin 1 receptor gene. In a pertinent study, researchers inhibited melanocortin 1 receptors utilizing natural inhibitors, resulting in diminished melanin synthesis and morphological heterogeneity in murine B16-F10 melanoma cells. Notably, this inhibition correlated with decelerated tumor cell growth and enhanced uniformity in tumor size and morphology.

The findings underscore the potential significance of melanocortin 1 receptors in governing melanoma growth and morphology, suggesting that sustained inhibition of these receptors might impede the growth rate of tumor cells expressing them. It is noteworthy that Nonapeptide-1’s impact on melanoma tumor cells remains unexplored.


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.



  1. Ishihara Y, Oka M, Tsunakawa M, Tomita K, Hatori M, Yamamoto H, Kamei H, Miyaki T, Konishi M, Oki T. Melanostatin, a new melanin synthesis inhibitor. Production, isolation, chemical properties, structure and biological activity. J Antibiot (Tokyo). 1991 Jan;44(1):25-32. doi: 10.7164/antibiotics.44.25. PMID: 1672125.
  2. MelanostatineTM 5 – Lucas Meyer Cosmetics – datasheet. Available at:
  3. Abu Ubeid A, Zhao L, Wang Y, Hantash BM. Short-sequence oligopeptides with inhibitory activity against mushroom and human tyrosinase. J Invest Dermatol. 2009 Sep;129(9):2242-9. doi: 10.1038/jid.2009.124. Epub 2009 May 14. PMID: 19440221.
  4. Chen, J., Li, H., Liang, B., & Zhu, H. (2022). Effects of tea polyphenols on UVA-induced melanogenesis via inhibition of α-MSH-MC1R signalling pathway. Postepy dermatologii i alergologii, 39(2), 327–335.
  5. Mohammed, Y. H., Moghimi, H. R., Yousef, S. A., Chandrasekaran, N. C., Bibi, C. R., Sukumar, S. C., Grice, J. E., Sakran, W., & Roberts, M. S. (2017). Efficacy, Safety and Targets in Topical and Transdermal Active and Excipient Delivery. Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin: Methodology and General Considerations, 369–391.
  6. Chatterjee, M., Neema, S., & Rajput, G. R. (2021). A randomized controlled pilot study of a proprietary combination versus sunscreen in melasma maintenance. Indian journal of dermatology, venereology and leprology, 88(1), 51–58.
  7. Xia Y, Wikberg JE, Chhajlani V. Expression of melanocortin 1 receptor in periaqueductal gray matter. Neuroreport. 1995 Nov 13;6(16):2193-6. doi: 10.1097/00001756-199511000-00022. PMID: 8595200.
  8. Delaney, A., Keighren, M., Fleetwood-Walker, S. M., & Jackson, I. J. (2010). Involvement of the melanocortin-1 receptor in acute pain and pain of inflammatory but not neuropathic origin. PloS one, 5(9), e12498.
  9. Kansal, R. G., McCravy, M. S., Basham, J. H., Earl, J. A., McMurray, S. L., Starner, C. J., Whitt, M. A., & Albritton, L. M. (2016). Inhibition of melanocortin 1 receptor slows melanoma growth, reduces tumor heterogeneity and increases survival. Oncotarget, 7(18), 26331–26345.
CJC-1295 and Ipamorelin Peptide Blend – Scientific Observations

CJC-1295 and Ipamorelin Peptide Blend – Scientific Observations

Ipamorelin and CJC-1295 peptides are classified as growth hormone secretagogues. Ipamorelin is a synthetic pentapeptide, while CJC-1295 is composed of 29 amino acids. Ipamorelin falls within the classification of peptides known as growth hormone secretagogues (GHSs), which are presumed to stimulate the release of growth hormones without being growth hormone releasing peptides themselves.[1] Conversely, researchers have suggested that CJC-1295 may potentially stimulate growth hormone release by emulating the actions of endogenous growth hormone-releasing hormone (GHRH).[2]

Both Ipamorelin and CJC-1295 peptides are grouped within this category, investigated for their supposed similar physiological effects, although they appear to differ primarily in their half-life and pharmacokinetic properties.


CJC-1295 Peptide

CJC-1295 peptide represents a tetra-substituted derivative of growth hormone-releasing hormone (GHRH) 1-29, devised to mimic the shortest functional sequence of GHRH. GHRH 1-29 encompasses the initial 29 amino acids of the native GHRH peptide and holds the potential to stimulate growth hormone production within somatotrophs, the pituitary gland cells. The peptide undergoes four amino acid substitutions, strategically positioned within its structure, which researchers hypothesize may bolster its activity and resilience against proteolytic degradation. Specifically, the substitutions are situated at the 2nd, 8th, 15th, and 27th amino acid positions.

These alterations potentially enable the peptide to covalently bind to blood albumin, with incidental interactions possibly occurring with fibrinogen and immunoglobulin G (IgG). Consequently, the reported half-life of the peptide may possibly extend from 10 minutes to approximately 30 minutes.[3] This elongated half-life may culminate in heightened levels of plasma growth hormone and insulin-like growth factor 1 (IGF-1).

Furthermore, CJC-1295 is speculated to incorporate a “drug affinity complex” (DAC) component, which may associate with plasma proteins. Specifically, the DAC element within CJC-1295 pertains to the attachment of N-epsilon-3-maleimidopropionamide derivative of lysine at the C-terminal end. By amalgamating the tetra-substituted amino acid chain with the DAC element, CJC-1295 may exhibit improved pharmacokinetic properties while preserving a comparable affinity to the GHRH receptors within the pituitary gland, akin to endogenous GHRH.[4]


Ipamorelin Peptide

Ipamorelin is a synthetically engineered pentapeptide believed to interact with the growth hormone secretagogues receptor (GHS-R1a) situated in pituitary gland cells. These receptors, primarily localized in the hypothalamus, are commonly referred to as ghrelin receptors due to the apparent affinity of ghrelin as their primary endogenous ligand. Ipamorelin distinguishes itself among other growth hormone secretagogues (GHSs) as a potentially more selective compound. It is hypothesized to selectively stimulate the release of growth hormone (GH) levels from somatotroph cells without concomitant elevation of other hormones produced by the anterior pituitary gland, such as prolactin.

When the peptide blend, also denoted as the peptide stack, is introduced in combination, studies indicate that Ipamorelin typically initiates first action, purported exhibiting discernible impact within the initial two hours of exposure. Subsequently, as the Ipamorelin effect diminishes, the CJC-1295 peptide may progressively contribute to the alleged physiological actions.[5]


CJC-1295 & Ipamorelin Peptide Blend and Growth Hormone Levels

In a clinical trial[6] conducted in the early 2000s, research subjects were allocated into two groups: one receiving a placebo and the other exposed to CJC-1295 peptide. Blood samples taken before and after the peptide exposure revealed a substantial increase, approximately 7.5-fold, in growth hormone pulsatility levels in the CJC-1295 group compared to the placebo group. Additionally, beyond its apparent influence on growth hormone synthesis, CJC-1295 reportedly “caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as [noted] by immunohistochemistry images.”

The underlying mechanisms of CJC-1295’s potential reportedly involve its interaction with specific binding sites on the growth hormone-releasing hormone (GHRH) receptor protein, possibly triggering conformational changes and initiating intracellular signaling cascades.[7] This interaction is speculated to activate G-proteins, which, in turn, may lead to the generation of secondary messengers like cyclic adenosine monophosphate (cAMP) or inositol trisphosphate (IP3). These messengers further modulate cellular activities through protein kinases, ultimately influencing gene expression associated with growth hormone production.

Conversely, researchers suggest that Ipamorelin interacts with the N-terminus of the growth hormone secretagogue receptor (GHS-R1a) in anterior pituitary gland cells, forming non-permanent attachments through intermolecular forces such as hydrogen bonds and van der Waals forces. This interaction may potentially induce conformational changes in the receptor, initiating cell signaling pathways primarily involving G-proteins, notably Gαq/11.[8] Activation of GHS-R1a may potentially trigger the activation of phospholipase C (PLC), leading to the production of secondary messengers like IP3 and diacylglycerol (DAG). IP3 release may lead to calcium ion (Ca2+) release from the endoplasmic reticulum, while DAG activates protein kinase C (PKC), ultimately facilitating the release of growth hormone from pituitary gland cells.[9]

These findings suggest the intricate molecular mechanisms through which CJC-1295 and Ipamorelin may potentially modulate growth hormone secretion, providing valuable insights into their possible physiological effects.


Comparative Mechanisms of Action

Research investigations have been undertaken to ascertain the half-life and individual mechanistic actions of the two peptides – Ipamorelin and CJC-1295.

In a 1990s study[5] with a concentration-escalation design, the levels of growth hormones were systematically monitored following each presentation of the peptides. The study’s findings suggested a singular episode of growth hormone release, reaching its zenith at 0.67 hours, followed by an exponential decline, supposedly due to negligible concentrations. This investigation concluded that Ipamorelin appears to exhibit a short half-life of approximately 2 hours, with potential actions tapering off thereafter.

In contrast, CJC-1295 was suggested to host a notably protracted half-life. Researchers noted that a single introduction of the peptide appeared to have led to sustained upregulation of growth hormone production by somatotrophs, purportedly contributing to an overall increase in growth hormone secretion by 46%. Another publication reported potential increases in growth hormone concentrations by “2- to 10-fold” and estimated the half-life of CJC-1295 to range between 5.8 to 8.1 days.[11]


Ipamorelin & CJC-1295 Peptide Blend and Lean Mass

The interaction between CJC-1295 and Ipamorelin in stimulating growth hormone production by somatotroph cells in the anterior pituitary gland appears to yield a synergistic effect, potentially resulting in a positive nitrogen balance and increased lean mass in experimental models. A study[11] aimed to elucidate the metabolic potential of Ipamorelin focused on hepatic markers associated with alpha-amino-nitrogen processing during artificially-induced catabolism.

Researchers investigated the liver’s capacity to produce urea-N (CUNS), serving as an indicator of nitrogen processing within the organ. They assessed the mRNA levels associated with enzymes of the urea cycle, evaluated overall nitrogen equilibrium, and estimated nitrogen distribution across various organs. Ipamorelin exposure was hypothesized to lead to a notable 20% reduction in CUNS compared to the catabolic state induced experimentally. Additionally, it was suggested that Ipamorelin might decrease the expression of urea cycle enzymes, restore nitrogen equilibrium, and potentially modulate nitrogen levels in organs.


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.



  1. 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.
  2. Lucie Jette et al, hGRF1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long Lasting GRF Analog, ResearchGate, January 2005.
  3. The Discovery of Growth Hormone-Releasing Hormone: An Update
  4. 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.
  5. Gobburu JV, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999 Sep;16(9):1412-6. doi: 10.1023/a:1018955126402. PMID: 10496658.
  6. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006 Dec;91(12):4792-7. doi: 10.1210/jc.2006-1702. Epub 2006 Oct 3. PMID: 17018654.
  7. Martin, B., Lopez de Maturana, R., Brenneman, R., Walent, T., Mattson, M. P., & Maudsley, S. (2005). Class II G protein-coupled receptors and their ligands in neuronal function and protection. Neuromolecular medicine, 7(1-2), 3–36.
  8. Yin, Y., Li, Y., & Zhang, W. (2014). The growth hormone secretagogue receptor: its intracellular signaling and regulation. International journal of molecular sciences, 15(3), 4837–4855.
  9. Bill, C. A., & Vines, C. M. (2020). Phospholipase C. Advances in experimental medicine and biology, 1131, 215–242.
  10. Martin, B., Lopez de Maturana, R., Brenneman, R., Walent, T., Mattson, M. P., & Maudsley, S. (2005). Class II G protein-coupled receptors and their ligands in neuronal function and protection. Neuromolecular medicine, 7(1-2), 3–36.
  11. Aagaard, N. K., Grøfte, T., Greisen, J., Malmlöf, K., Johansen, P. B., Grønbaek, H., Ørskov, H., Tygstrup, N., & Vilstrup, H. (2009). Growth hormone and growth hormone secretagogue effects on nitrogen balance and urea synthesis in steroid treated rats. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 19(5), 426–431.
Protirelin (TRH Thyrotropin ) – General Research and Scientific Observations

Protirelin (TRH Thyrotropin ) – General Research and Scientific Observations

Protirelin (TRH Thyrotropin) is a synthetic analog peptide of the naturally occurring thyrotropin-releasing hormone (TRH). It comprises three amino acids and is considered by scientists to be released by the brain’s hypothalamus region. As such, it is classified as a neuropeptide with potential neuromodulation characteristics. This peptide has also been studied for its potential to assess abnormal thyroid gland functioning for diagnostic purposes. According to the data from the National Library of Medicine and National Center for Biotechnology Information, Protirelin may potentially have implications in thyroid/pituitary abnormalities, and spinocerebellar degeneration (SCD). Protirelin has also been explored by researchers within the diagnosis of thyroid gland functions, which may potentially be due to chemical signaling among the hypothalamus, pituitary, and thyroids.


Protirelin Essential Functions

Researchers suggested that Protirelin may mimic the characteristics of naturally-occurring thyrotropin-releasing hormone (TRH). TRH is considered the first well-characterized hypothalamic peptide and has been studied as a neuroendocrine element. This peptide appears to be widely distributed in different brain regions, alluding to its analogs’ potential within the context of conditions such as brain and spinal injuries, as well as CNS disorders like schizophrenia, Alzheimer’s disease, epilepsy, amyotrophic lateral sclerosis, Parkinson’s disease, depression, shock, and ischemia.

Protirelin appears to stimulate the release of thyroid-stimulating hormone from the anterior pituitary. Additionally, it may potentially also increase prolactin release. The peptide has been suggested to increase TSH levels rapidly, peaking, then proceeding to decline more slowly, returning to baseline levels after about three hours.


Scientific Studies on Protirelin

Research teams have evaluated the potential impacts of Protirelin in the context of spinocerebellar degeneration (SCD). This disease is manifested as a group of progressive neurodegenerative disorders affecting the spinal cord and cerebellum, vital central nervous system components. Research models of SCD ultimately exhibit a decline in motor function. The potential efficacy of the peptide within the context of SCD was assessed using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Data from both these scoring matrices may indicate the effectiveness of Protirelin in ameliorating SCD.[1]

Thyrotropin releasing hormone (TRH), the smallest peptide hormone, is considered to exhibit central effects beyond its endocrine potential by acting on the pituitary-thyroid axis. It has been suggested to hold potential within the context of various neurological disorders, including intractable epilepsy. Research has been conducted to evaluate this peptide within the context of conditions like West syndrome, Lennox-Gastaut syndrome, and myoclonic epilepsy. Protirelin’s hypothetically prolonged action suggests a unique anticonvulsant mechanism, potentially influencing the seizure network’s plasticity.[2]


Case Studies of Protirelin

In a randomized, single-blind, placebo-controlled study, research models of chronic upper motoneuron syndrome due to ischemic cerebrovascular lesions were exposed to a Protirelin tartrate. A semiquantitative assessment was used to identify a homogenous sample population, focusing on weakness and spasticity and neurophysiological evaluations (F-waves, magnetic motor evoked potentials). Results suggested a statistically significant absolute improvement in spasticity and muscular strength following the Protirelin tartrate, particularly in the lower limbs. The compound also exhibited supposedly favorable modifications in the response of the biceps femoris muscle to transcranial magnetic stimulation, including reappearance, increased amplitude, and a reduction in the motor-evoked potential threshold.[3]

Exposure of L-pyroglutamyl-L-histidyl-L-prolinamide (protirelin) to research models of amyotrophic lateral sclerosis (ALS), appeared to result in an improvement in functions associated with a deficiency in both lower motor neurons (weakness) and upper motor neurons (spasticity). This improvement appeared to be sustained during the infusion and persisted for about 1 hour post-infusion, with occasional slight improvements even 20 hours later. The mechanism by which Protirelin may produce this action, whether by replacing an ALS-associated deficiency or acting as a symptomatic supplement, remains uncertain. This study suggests the potential of further TRH study within the context of ALS, and offers insights into its potential pathogenesis, opening avenues for further exploring this biomolecule.[4]

Researchers hypothesize that Protirelin is also involved in elevating prolactin plasma levels, which may potentially influence sexual drive and function. As such, elevation in prolactin with Protirelin may contribute to modulating central nervous system centers regulating sexual drive and behavior.[7]



Protirelin is a synthetic analog of the TRH neuropeptide. As outlined above, researchers speculate that the peptide’s impact may be diverse, the most prominent being neuroprotective potential in several neurodegenerative diseases. This peptide appears to be widely distributed in the hypothalamus region and may potentially manifest mitigatory action in refractory epilepsy, amyotrophic lateral sclerosis, motoneuron syndrome, and spinocerebellar degeneration.[8]


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.



  1. Yoshida A, Yamanishi Y, Tada S, Miyaue N, Ando R, Nagai M. Comparison of therapeutic effectiveness with SARA and iCARS using protirelin for spinocerebellar degeneration’s patients. Neurological Therapeutics. 2022;39(5):803-807. doi:10.15082/jsnt.39.5_803
  2. Takeuchi Y. Thyrotropin-Releasing Hormone (Protirelin). CNS Drugs. 1996;6:341–350.
  3. Civardi C, Naldi P, Cantello R, Gianelli M, Mutani R. Protirelin tartrate (TRH-T) in upper motoneuron syndrome: a controlled neurophysiological and clinical study. Ital J Neurol Sci. Nov 1994;15(8):395-406. doi:10.1007/BF02339903, PMID: 7875957,
  4. Engel WK, Siddique T, Nicoloff JT. Effect on weakness and spasticity in amyotrophic lateral sclerosis of thyrotropin-releasing hormone. Lancet. Jul 9 1983;2(8341):73-5. doi:10.1016/s0140-6736(83)90060-0, PMID: 6134961,
  5. Eandi M, Signorile F, Rubinetto MP, Genazzani E. [Evaluation of the efficacy and tolerability of protirelin. Results of a multicenter study in Italy]. Ann Ital Med Int. Jul-Sep 1990;5(3 Pt 2):270-8. Valutazione dell’efficacia e tollerabilita della protirelina. Risultati di uno studio policentrico in Italia. PMID: 2127689,
  6. Marangell LB, George MS, Callahan AM, Ketter TA, Pazzaglia PJ, L’Herrou TA, Leverich GS, Post RM. Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients. Arch Gen Psychiatry. Mar 1997;54(3):214-22. doi:10.1001/archpsyc.1997.01830150034007, PMID: 9075462,
  7. Kruger TH, Haake P, Haverkamp J, Kramer M, Exton MS, Saller B, Leygraf N, Hartmann U, Schedlowski M. Effects of acute prolactin manipulation on sexual drive and function in males. J Endocrinol. Dec 2003;179(3):357-65. doi:10.1677/joe.0.1790357, PMID: 14656205,
  8. Alvarez-Salas E, Garcia-Luna C, de Gortari P. New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent. Int J Mol Sci. Jul 4, 2023;24(13) doi:10.3390/ijms241311047, PMID: 37446225 PMCID: PMC10341491,