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GHRP-2: An overview of the current research

GHRP-2 Serum murine GH responses to 10 µg GHRP-2 (or saline (SAL)) in lit/lit (i.e. GHRH-deficient) mice in comparison to heterozygous or WT animals. From Peroni et al., Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient little mice. Clinics (Sao Paulo). 2012;67(3):265-272.

 

What is GHRP-2?

GHRP-2 is a small peptide (made of six amino acids) associated with the release of growth hormone (GH)1. This protein is associated with important roles in the regulation of sex hormones and metabolic control2. Decreases in this hormone are also associated with reductions in muscle mass, bone deterioration and possible cognitive deficits3. It is also linked to the increased risk of death from cardiovascular disease3. Growth hormone, as the name suggests, also plays a role in the growth and development of humans and other animals. GH deficiency has been shown to result in growth retardation.

 How does GHRP-2 act to increase GH?

The release of GH is stimulated by the GH secretagogue (GHS) receptor, which is normally activated by ghrelin (also known as the GHS). GHRP-2 is a synthetic peptide that has also been shown to activate the GHS receptor (GHS-R1a)4. GHRP-2 (and ghrelin) also stimulates the release of prolactin, corticotropin and cortisol4. This has a positive effect on energy expenditure, appetite, heart muscle tone and sleep regulation. There is also a GH-releasing hormone (GHRH) present in humans and other animals, which stimulates the release of GH through its own receptor (GHRH-R). GHRP-2 complements this by potentiating the cAMP activation associated with GHRH-R binding, and may also promote the population of this receptor4. GHRP-2 has been found to significantly increase GH in genetically GHRH-deficient mice4. GHRP-2 is also associated with increases in IGF15.

Other functions and uses of GHRP-2

GHRP-2 may be administered orally. However, this is linked to reduced efficacy, as oral formulations have been found to result in poor absorption and thus reduced effects on (for example) GH secretion6. Intravenous solutions of GHRP-2 are regarded as the standard route, although subcutaneous and intraperitoneal administration is also used in some trials5-7. GHRP-2 may also have a potential role in analgesia (pain relief). This is due to recent observations that GHS-R1a activation by ghrelin in mice resulted in analgesia8. A recent study found that GHRP-2 also produced these effects. This was shown to be reversed by naloxone administration, indicating that GHS-R1a may be able to affect opioid receptors in the central nervous system8.

GHRP-2 has also been found to bind to C36, which is a receptor for the pro-athergenic oxidized low-density lipoprotein5. It was found to reduce oxidative stress, but not plaque size, in a mouse model of atherosclerosis5. Subcutaneous GHRP-2 resulted in improvements of a rat model of acute lung injury9. This was attributed to reductions in TNFalpha, IL-6 and NFkappaB in the lung tissue of GHRP-2-treated rats9. This is further evidence of the anti-inflammatory properties of this peptide.

Another study found that TNFalpha was also reduced by intraperitoneal GHRP-2 in a rat model of liver damage7. To confirm that this was as a result of exogenous GHRP-2, these researchers administered endotoxins and GHRP-2 to cultures of hepatocytes and nonparenchymal cells with hepatocytes. The peptide caused a reduction in TNFalpha mRNA in the latter, but not the former7. This indicates that GHRP-2 acts directly on the liver through nonparenchymal cells to reduce inflammation.

 References:

1. Bowers CY. GH releasing peptides--structure and kinetics. J Pediatr Endocrinol. 1993;6(1):21-31.

2. Veldhuis JD, Roemmich JN, Richmond EJ, Bowers CY. Somatotropic and gonadotropic axes linkages in infancy, childhood, and the puberty-adult transition. Endocr Rev. 2006;27(2):101-140.

3. Norman C, Rollene NL, Erickson D, Miles JM, Bowers CY, Veldhuis JD. Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone and somatostatin in postmenopausal women. Eur J Endocrinol. 2014;170(1):121-129.

4. Peroni CN, Hayashida CY, Nascimento N, et al. Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient little mice. Clinics (Sao Paulo). 2012;67(3):265-272.

5. 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;150(12):5478-5487.

6. Tanaka T, Hasegawa Y, Yokoya S, Nishi Y. Increased Secretion of Endogenous GH after Treatment with an Intranasal GH-releasing Peptide-2 Spray Does Not Promote Growth in Short Children with GH Deficiency. Clin Pediatr Endocrinol. 2014;23(4):107-114.

7. Granado M, Martin AI, Lopez-Menduina M, Lopez-Calderon A, Villanua MA. GH-releasing peptide-2 administration prevents liver inflammatory response in endotoxemia. American journal of physiology. Endocrinology and metabolism. 2008;294(1):E131-141.

8. Zeng P, Li S, Zheng Y-h, et al. Ghrelin receptor agonist, GHRP-2, produces antinociceptive effects at the supraspinal level via the opioid receptor in mice. Peptides. 2014;55:103-109.

9. Li G, Li J, Zhou Q, Song X, Liang H, Huang L. Growth hormone releasing peptide-2, a ghrelin agonist, attenuates lipopolysaccharide-induced acute lung injury in rats. The Tohoku journal of experimental medicine. 2010;222(1):7-13. 

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