Complete Guide to GHRP-2 Peptide
There are various synthetic and natural peptides that help stimulate the secretion of growth hormones in the body, and thereby maintain their equilibrium. One such synthetic peptide is called Pralmorelin, or more commonly GHRP-2.
Growth hormones play a vital role in adult humans in regulating body growth and development, maintaining metabolic rate and bodily functions such as the cardiovascular system, cognitive functions and enhancing lipid metabolism.
However, as people age, the levels of growth hormones decline from 150 microg per kg body weight to 25 microg per kg body weight by the age of 55 (1). Besides this, growth hormone deficiency (GHD) is also a known disorder. In both cases, with the decreased concentrations of growth hormones, the ability of the body to perform normal functions also decreases.
What is GHRP-2?
GHRP-2 is a synthetic peptide that is analogous to the endogenous peptide called ghrelin (1). Ghrelin is a naturally occurring peptide, first isolated from the stomach, composed of 28 amino acids and helps regulate food intake, growth hormone release and wound recovery (11).
As the name suggests, growth hormone releasing peptide GHRP 2 stimulates the secretion of human growth hormones (HGH) in the body and helps maintain the required HGH concentrations in the body.
The ghrelin system was first discovered in the early 1970s (3).
Between 1970 and 2000, there were many discoveries of the growth hormone releasing peptides (GHRP) and their isolation studies.
During the initial period, it was believed that GHRPs function same as GHRH i.e., growth hormone releasing hormone. However, between 1982 and 1984, during comparisons between GHRP and GHRH, it was understood that GHRPs are in fact pleiotropic peptides having significant effects on growth hormones, metabolism as well as increased food intake.
While the primary function of GHRP remains associated with maintaining the growth hormone levels, it also regulates nutrition and metabolism functions. Various studies have demonstrated that GHRP and ghrelin have the same effect on GH secretion in both rats and humans (3).
Functioning of GHRP-2 peptide
Bovine studies have suggested that GHRP-2 peptide exerts its effects through the following ways (4):
- Acts on the pituitary cells and stimulates secretion of GH
- May bind with growth hormone release factor (GRF) receptor
- Acts on calcium channels, stimulates secretion of calcium and induces GH release due to calcium influx
- Stimulates cAMP pathway and protein kinase C, which increase GH secretion
As shown in the above image, when GHRP-2 is administered in the body, it binds with the receptor, stimulating adenyl cyclase activity. This results in cAMP production and activation of protein kinase. Both these elevated levels of cAMP and protein kinase lead to increased calcium influx and subsequent growth hormone secretion (5).
GHRP-2 Uses or Benefits
As with other growth hormone release stimulating peptides, GHRP-2 demonstrates similar effects which are as follows:
- Increased growth hormone levels
- Elevated body muscle mass
- Enhanced flexibility
- Improved joint health
- Improved sleep
- Potential anti-aging effects
- Increased strength and endurance
GHRP-2 results in higher growth hormone levels, which in turn lead to higher IGF-1 concentrations in the body. Higher IGF-1 leads to acceleration in growth of muscle tissues and reduction in body fat – all of which are added advantages of the peptide listed above.
Research and Clinical studies
General Pharmacological Effects
Various studies (6) have been conducted on animals to understand the pharmacological effects of GHRP-2 peptide.
The administration of the GHRP-2 peptide in both rabbits and guinea pigs showed no noticeable effect on the central nervous system. There was no other significant effect besides slight increase in the motility of the isolated rabbit ileum and increased contraction of the isolated guinea pig ileum, at high GHRP-2 doses. There were no effects on the respiratory, digestive, renal and blood system after the peptide administration.
This study demonstrated that GHRP-2 led to no other serious pharmacological effects when administered at growth hormone releasing dose levels. This was indicative of the fact that the peptide could potentially be useful for the treatment of GH deficiency.
GHRP-2 Effects on Body Hormones
This study (7) was conducted to understand the effects of two synthetic GHRPs namely GHRP-2 and Hexarelin (HEX) on growth hormones, prolactin, adrenocorticotropic hormone (ACTH) and cortisol concentration in men.
Two subject groups were studied – one, with 6 young adults aged between 22 and 27 years and the second, with 6 elderly individuals aged between 66 and 73 years.
The young group was administered with 1 microg/kg and 2 microg/kg body weight of GHRP-2 and HEX via intravenous route, and the elderly group was treated with only 2 microg/kg dose via the same route. The results were then compared with the GHRH (growth hormone releasing hormone) treated candidates.
The GH levels in young adults was higher in 2 microg/kg dose of GHRP-2 when compared to the 1 microg/kg dose. These results were similar to that of HEX treated patients. However, when compared to the GH levels of the GHRH treated candidates, both GHRP-2 and HEX demonstrated higher levels of GH than GHRH.
Similarly, in elderly patients, both GHRP-2 and HEX resulted in higher levels of GH compared to GHRH, but lower than those in the young candidates.
All doses of HEX and GHRP-2 demonstrated similar effects on the other ACTH and cortisol hormones as well. Whereas, it also stimulated increased concentrations of prolactin, however the levels were not as significantly high as others.
This study demonstrated that GHRP-2 and HEX stimulated dose and age dependent similar effects on growth hormone secretion in men.
Increased Food Intake
In this study (2), 7 healthy males were divided into two subject groups, one of which was administered with GHRP-2 (1 microg per kg per hour) and the other with saline for 4.5 hours via subcutaneous route of administration. They were then taken to a buffet meal to measure their food intake.
It was noted that the GHRP-2 infused candidates ate almost 36% more than the saline treated candidates, with every subject reportedly showing increased food intake when measured against their respective bodyweight. Furthermore, the GH levels also showed a significant increment where GHRP-2 infused candidates GH levels were 5550 microg/L per 240 min whereas it was 412 microg/L per 240 min for the saline treated candidates.
Hence, this indicated that GHRP-2 intake leads to appetite increase and can potentially be used to investigate ghrelin effects in humans with respect to food intake.
GH Deficiency Diagnosis in Adults
The most common diagnostic tool for GH deficiency in adults is insulin tolerance test (ITT), which may cause severe adverse effects in some patients and can be contradictory. The alternative suggested was to use GHRPs, and this study (8) aims to validate the use of GHRP-2 as a diagnostic tool for GH deficiency in adults.
135 patients were included in this study (8), who were first tested via ITT. 77 were healthy and 58 showed GH peak levels of less than 3.
Post overnight fasting, all candidates were intravenously administered with 100 microg dose of GHRP-2. After 2 hours, their blood samples were collected and tested.
Upon analysis, it was noted that the GH levels peaked after 1 hours of GHRP-2 administration in all candidates. While it was not gender affected, but the effects were slightly lower in patients with more weight (obese) and old age. These results were reproducible upon repeating the tests. The GH levels were significantly higher in healthy candidates as compared to the patients.
This study demonstrated that GHRP-2 can be used for the diagnosis of severe GH deficiency in patients, with slight influence by age and adiposity levels. Furthermore, based on the results, the optimal diagnostic dose of GHRP-2 was determined to be 15 microg/L.
GHRP-2 Diagnostic Effects on GH Deficient Children
This study (9) was conducted to demonstrate the diagnostic effects of GHRP-2 on children with GH deficiency (GHD) in comparison to the conventional medications (arginine, L-dopa, etc.)
24 children suffering from GHD were enrolled in this study. All children were treated with at least one conventional medication and were to be treated with GHRH and GHRP-2 in this study via intravenous and intranasal route.
All children were first administered with intravenous GHRP-2. When measured, the serum GH levels had significantly increased in these children. 21 children who demonstrated a more robust response to the treatment were then treated with GHRP-2 and GHRH simultaneously via an intravenous route. All children demonstrated a combined effect of the two agents on their serum GH levels. 15 of these 21 children were then administered with GHRP-2 via intranasal route, with a dose ranging from 5 to 20 microg per kg. The results showed a highly significant response in their GH levels.
This study demonstrated that both intravenous and intranasal administration of GHRP-2 were well tolerated in children. The added advantage of the GHRP-2 administration was that it proved to be a reliable predictor of the pituitary gland’s capacity to release GH, which was not so with the conventional medications.
Combination study with TRH and GnRH
This study (10) was conducted on patients with prolonged critical illness suffering from hyposomatotropism, hypogonadism, and hypothyroid and to evaluate the effects of combination treatment with GHRP-2, Thyrotropin releasing hormone (TRH) and Gonadotropin releasing hormone (GnRH) with GHRP-2 alone and with GHRP-2 and TRH co-administration.
33 male patients with critical illness were enrolled in this study based on the study protocol. For 5 days, 7 patients were administered with placebo, 9 were administered with 1 microg per kg dose of GHRP-2 every hour, 9 patients with hourly administration of GHRP-2 and TRH at 1+1 microg per kg dose and the remaining with GHRP-2 + TRH and GnRH at the dose of 0.9 microg per kg every 90 minutes. Serum samples were collected on the first and last night of the treatment.
After the results were analyzed, it was determined that the combination treatment of GHRP-2, GnRH and TRH induced reactivation of growth hormones, thyroid stimulating hormone and luteinizing hormone axis, along with other beneficial metabolic effects. These effects were absent with GHRP-2 solo administration and only partially seen with GHRP-2 and TRH co-administration.
Side Effects of GHRP-2
Studies (6) have demonstrated a safe profile of the peptide indicating that GHRP-2 is a well-tolerated peptide.
There are some minor side effects that may occur depending on the individual patient profile including but not limited to:
- Increased appetite
- Hot flushes
- Pain, redness and swelling at the site of administration (if administered via injection)
- Fatigue, lethargy
GHRP-2 Peptide Profile
The above listed studies have demonstrated that GHRP-2 is a safe, well-tolerated peptide with minimal side effects known to date. As indicated in the listed studies, GHRP-2 can be administered via intravenous and intranasal routes. There are also studies (12) conducted on research animals demonstrating that GHRP-2 can also be administered orally showing similar results.
Mainly used as a diagnostic tool for GHD, the optimal diagnostic dose of GHRP-2 for adults was determined to be 15 microg/L (8).
As with other medications, the therapeutic dose may vary amongst individuals depending on the individual profile. Besides, studies are still ongoing to demonstrate the full potential of GHRP-2 and its efficacy as a potent therapeutic medication.
Synonyms/Aliases: GHRP-2, Pralmorelin, Growth Hormone-Releasing Peptide 2, pralmorelin dihydrochloride
GHRP-2 is a potent peptide that mimics the effects of the endogenous 28-amino acid peptide called ghrelin.
The peptide stimulates growth hormone release in the system by either acting on the pituitary gland or by activating the cAMP pathway and protein kinase synthesis, which thereby leads to increased serum GH concentrations.
GHRP-2 has shown promising results in diagnostic studies and is now used as a diagnostic tool for GH deficient children and adults.
That being said, GHRP-2 also induces increased levels of energy and stamina due to which people, especially athletes, tend to abuse it as a doping agent. Owing to this, GHRP-2 is strictly prohibited in sports and is on an all-time sports ban at the World Anti-Doping Agency (WADA)(13).
While past studies have shown promising results, science does not stop. Continued research goes on for GHRP-2 to explore its full potency and use as a therapeutic agent in still more ailments.
1. Garcia JM, Merriam GR, Kargi AY. Growth Hormone in Aging. [Updated 2019 Oct 7]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com https://www.ncbi.nlm.nih.gov/books/NBK279163/
2. 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/
3. Bowers CY. History to the discovery of ghrelin. Methods Enzymol. 2012;514:3-32. doi: 10.1016/B978-0-12-381272-8.00001-5. PMID: 22975043. https://pubmed.ncbi.nlm.nih.gov/22975043/
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. https://pubmed.ncbi.nlm.nih.gov/9331879/
5. Asad Rahim, Stephen M. Shalet, in Growth Hormone Secretagogues, 1999. Does desensitization to growth hormone secretagogues occur? https://www.sciencedirect.com/topics/medicine-and-dentistry/pralmorelin
6. 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. https://pubmed.ncbi.nlm.nih.gov/15646371/
7. Emanuela Arvat, Lidia Di Vito, Barbara Maccagno, Fabio Broglio, Muni F Boghen, Romano Deghenghi, Franco Camanni, Ezio Ghigo, Effects of GHRP-2 and Hexarelin, Two Synthetic GH-Releasing Peptides, on GH, Prolactin, ACTH and Cortisol Levels in Man. Comparison with the Effects of GHRH, TRH and hCRH, Peptides, Volume 18, Issue 6, 1997, Pages 885-891, ISSN 0196-9781, https://doi.org/10.1016/S0196-9781(97)00016-8
8. Chihara K, Shimatsu A, Hizuka N, Tanaka T, Seino Y, Katofor Y; KP-102 Study Group. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency. Eur J Endocrinol. 2007 Jul;157(1):19-27. doi: 10.1530/EJE-07-0066. https://pubmed.ncbi.nlm.nih.gov/17609397/
9. Pihoker C, Middleton R, Reynolds GA, Bowers CY, Badger TM. Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature. J Clin Endocrinol Metab. 1995 Oct;80(10):2987-92. https://pubmed.ncbi.nlm.nih.gov/7559885/
10. 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. https://pubmed.ncbi.nlm.nih.gov/12030918/
11. GHRP 2, GPA 748, Growth Hormone-Releasing Peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102 LN. https://link.springer.com/article/10.2165/00126839-200405040-00011#
12. Phung LT, Sasaki A, Lee HG, Vega RA, Matsunaga N, Hidaka S, Kuwayama H, Hidari H. Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine. Domest Anim Endocrinol. 2001 Jan;20(1):9-19. https://pubmed.ncbi.nlm.nih.gov/11164330/
13. 2021 WADA Prohibited list. https://www.wada-ama.org/en/
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Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.