GHRP-2 (10mg)

GHRP-2 Peptide

GHRP-2, also known as Pralmorelin (also available in 5mg), is a synthetic growth hormone secretagogue that interacts with the ghrelin/growth hormone secretagogue receptor. It is a research peptide studied to evaluate growth hormone deficiency and secondary adrenal failure. GHRP-2, a pentapeptide composed of five amino acids, is similar in structure to the naturally occurring neurotransmitter met-enkephalin. However, it seems that GHRP-2 does not exhibit properties typical of neurotransmitters. Instead, it is thought to potentially interact with ghrelin receptors. Ghrelin, classified as an appetite-regulating hormone, may potentially be influenced by GHRP-2. It is suggested that this peptide may stimulate the production of growth hormone (GH) by potentially engaging with ghrelin receptors located on the pituitary gland, known as growth hormone secretagogue receptors (GHS-Rs). This interaction, however, remains speculative. Extensive research has also evaluated its role in regulating muscle cell development, the immune system, and sleep cycles.^[1]

Specifications

Other Known Titles: Thymosin Beta 4

Molecular Formula: C₄₅H₅₅N₉O₆

Molecular Weight: 817.9 g/mol

Sequence: H-D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2

GHRP-2 Research

GHRP-2 and the Pituitary Gland

The primary action of GHRP-2 appears to be linked to its interaction with Growth Hormone Secretagogue Receptors (GHS-Rs), which are activated by ghrelin. These receptors are distributed across various regions of the nervous system and other tissues, including the hypothalamus and pituitary gland. When GHRP-2 binds to GHS-Rs, it is suggested to induce a structural change that initiates a series of intracellular signals, commonly mediated by G-proteins. This interaction may lead to the release of Gaq/11, a G-protein component, which may trigger further downstream signaling events. For instance, Phospholipase C (PLC) may cleave phosphatidylinositol 4,5-bisphosphate (PIP2) into the secondary messengers IP3 and DAG (diacylglycerol). IP3 is understood to stimulate the release of calcium ions, while DAG may activate Protein Kinase C (PKC), thereby amplifying the signaling pathway and supporting growth hormone secretion from pituitary cells. The process may also involve the activation of cyclic AMP (cAMP), considered crucial for cellular signaling, with elevated cAMP levels potentially amplifying the signaling cascade and promoting growth hormone synthesis in the somatotroph cells of the anterior pituitary gland. It is theorized, however, that GHRP-2 may cause immediate receptor desensitization following exposure, potentially reducing receptor sensitivity for up to four hours before this effect reverses.[2]

GHRP-2 Peptide and Growth Hormone Synthesis

Researchers have suggested that GHRP-2 may produce a greater increase in GH levels when introduced to somatotroph cells than the increase physiologically triggered by growth hormone-releasing hormone (GHRH). Some evidence also indicates that GHRP-2 might elevate ACTH and cortisol levels, which may similarly be produced by pituitary cells. Further research suggests that under laboratory conditions, GHRP-2 exposure may result in a notable enhancement of peak GH levels and mean pulsatile GH secretion from anterior pituitary cells, and may also increase the activity of mediators involved in the anabolic actions of GH, such as insulin-like growth factor-1 (IGF-1). One study implicated GHRP-2 in producing up to a 181-fold surge in GH production from anterior pituitary cells relative to baseline.[3] IGF-1 levels were also reported to rise from an average of 100 mcg/l at baseline to approximately 180 mcg/l in a separate experiment, with researchers reporting that the peptide had “stimulated pulsatile, rhythmic, and entropic GH secretion by more than 3-fold” compared to GHRH.[4]

GHRP-2 and Muscle Structure

Research conducted in yaks indicated that GHRP-2 may have stimulated muscle growth through two mechanisms — enhanced protein synthesis and accumulation, and reduced protein degradation.[5] The study suggested that GHRP-2 may help overcome natural growth limitations arising from food deprivation, adverse environmental conditions, and disease. Researchers noted that “GHRP-2 enhanced muscle protein deposition mainly by up-regulating the protein synthesis pathways.” A particularly significant observation was the potential of GHRP-2 to reduce muscle atrophy through suppression of atrogin-1 and MuRF1 proteins, which are understood to regulate muscle degradation pathways.

GHRP-2 and the Heart

Studies in fetal heart cell culture lines have proposed that GHRP-2 and its analogs — GHRP-1 and GHRP-6 — may help protect cardiac cells by reducing apoptosis, or programmed cell death.[6] The peptide appears to offer protection to cardiac muscle from reduced blood and nutrient supply, which may otherwise contribute to cardiac arrest. Research into Hexarelin, a GHRP-2 analog, has proposed that these peptides interact with a specific receptor, with CD36 hypothesized to play a significant role in capturing oxidized low-density lipoprotein (OxLDL). This potential interaction between GHRP-2 and CD36 may reduce cellular uptake of OxLDL, understood to contribute to the development of atherosclerosis and associated reductions in blood and nutrient supply. Research suggests GHRP-2 may reduce interferon-gamma levels by 66% in cultured aortic smooth muscle cells — a test model for reduced blood and nutrient supply. While GHRP-2 introduction did not appear to significantly alter the extent of atherosclerotic plaque coverage, researchers suggested it may have lowered superoxide production in blood vessels. Additionally, GHRP-2 reportedly reduced gene expression of 12/15-lipoxygenase by approximately 92% and decreased the expression of interferon-gamma and macrophage migration inhibitory factors. Observations in cultured aortic smooth muscle cells further suggest that GHRP-2 might inhibit OxLDL-induced peroxide production, prevent suppression of the IGF-I receptor, and potentially block apoptosis. In macrophages exposed to OxLDL, GHRP-2 was observed to reduce lipid accumulation, further underscoring its potential antioxidative and cardioprotective properties.[6]

GHRP-2 and the Immune System

Researchers suggest that GHRP-2 may enhance the functions of the thymus — an organ recognized for its role in protecting and maturing immune cells, particularly T lymphocytes.[7] T lymphocytes are considered essential for adaptive immunity and the organism’s capacity to combat complex infections. Thymic efficacy is understood to diminish over time, potentially resulting in tissue deterioration and reduced immune competence. In such contexts, GHRP-2 appears to hold potential for thymic rejuvenation, possibly promoting the number and diversity of T cells and supporting overall immune function.

GHRP-2 and Pain Perception

Researchers initially proposed that GHRP-2 may reduce pain associated with osteoarthritis in animal models through stimulation of growth hormone production and facilitation of damaged tissue repair. It has further been suggested that GHRP-2 may produce analgesic effects prior to tissue repair, potentially through an action on opioid receptors, of which four are currently recognized.[8] Compounds studied for their effects on opioid receptors typically mediate a non-selective action across all four receptor subtypes — an approach that may present challenges given the differential and diverse functions of each receptor. GHRP-2 appears to function as a selective opioid receptor agonist, binding specifically to receptors implicated in pain perception, reward system activation, and sedation.

GHRP-2 and Sleep Cycles

GHRP-2 has been proposed to influence sleep cycles, with researchers reporting that the peptide may extend the duration of sleep stages 3 and 4 by up to 50%, and may potentially improve REM sleep duration by approximately 20%.[9] It may further reduce deviation from normal sleep patterns. Research in this area is ongoing.

GHRP-2 and Appetite

By activating GHS-Rs across various regions of the nervous system, GHRP-2 may initiate a cascade of cellular processes that enhance the production of hunger-stimulating neuropeptides — specifically Neuropeptide Y (NPY) and Agouti-related peptide (AgRP) — both considered essential for managing energy balance and appetite regulation. Concurrently, GHRP-2 may reduce the release of melanocyte-stimulating hormone (alpha-MSH), an appetite-suppressant hormone, potentially contributing to increased hunger and food consumption. GHRP-2 may also influence the mesolimbic reward system — a brain pathway involved in regulating food cravings — possibly through activation of GHSR-1a receptors, theoretically amplifying appetite via cyclic adenosine monophosphate (cAMP) pathway activation, further implicating the peptide in the modulation of feeding behavior and reward-driven eating. Research indicated that models administered GHRP-2 consumed approximately 36% more food than control models, with energy intake per kilogram of body weight measured at 136.0 plus or minus 13.0 kJ/kg in the GHRP-2 group compared to 101.3 plus or minus 10.5 kJ/kg in controls. GH levels were also elevated in GHRP-2 models relative to saline controls, with hormone levels expressed as area under the curve (AUC) reaching up to 5550 plus or minus 1090 ug/L/240 min versus 412 plus or minus 161 ug/L/240 min.[10]

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. Phung LT, Inoue H, Nou V, Lee HG, Vega RA, Matsunaga N, Hidaka S, Kuwayama H, Hidari H. The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine. Domest Anim Endocrinol. 2000 Apr;18(3):279-91. doi: 10.1016/s0739-7240(00)00050-3. PMID: 10793268.
2. Sinha, D. K., Balasubramanian, A., Tatem, A. J., Rivera-Mirabal, J., Yu, J., Kovac, J., Pastuszak, A. W., & Lipshultz, L. I. (2020). Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Translational andrology and urology, 9(Suppl 2), S149–S159. https://doi.org/10.21037/tau.2019.11.30
3. 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
4. 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
5. 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.
6. Titterington JS, Sukhanov S, Higashi Y, Vaughn C, Bowers C, Delafontaine P. Growth hormone-releasing peptide-2 suppresses vascular oxidative stress in ApoE-/- mice but does not reduce atherosclerosis. Endocrinology. 2009 Dec;150(12):5478-87. doi: 10.1210/en.2009-0283. Epub 2009 Oct 9. PMID: 19819949; PMCID: PMC2795722.]
7. Chao YN, Sun D, Peng YC, Wu YL. Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells. Int J Mol Sci. 2016 Aug 19;17(8):1359. doi: 10.3390/ijms17081359. PMID: 27548147; PMCID: PMC5000754.
8. Zeng P, Li S, Zheng YH, Liu FY, Wang JL, Zhang DL, Wei J. Ghrelin receptor agonist, GHRP-2, produces antinociceptive effects at the supraspinal level via the opioid receptor in mice. Peptides. 2014 May;55:103-9. doi: 10.1016/j.peptides.2014.02.013. Epub 2014 Mar 4. PMID: 24607724.
9. Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev. 2018 Jan;6(1):45-53. doi: 10.1016/j.sxmr.2017.02.004. Epub 2017 Apr 8. PMID: 28400207; PMCID: PMC5632578.
10. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824650/