GHRP-2

GHRP-2, also known as pralmorelin and KP-102, is a synthetic hexapeptide that releases growth hormone by acting at the receptor for ghrelin. This listing is the 10 mg vial of white freeze-dried powder, the main fill of the GHRP-2 range, and a 5 mg vial is also sold. Studies of GHRP-2 cover its origin in Cyril Bowers' peptide series, its use as a test of pituitary growth hormone reserve, how quickly it clears in children and its effect on food intake in men.

Sequence, and how it differs from GHRP-6

Written out in three-letter code, the sequence on the lot certificate is H-D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2. Three of the six residues are D-amino acids, the C-terminus is an amide, and position 2 holds D-2-naphthylalanine, a synthetic aromatic residue that proteins do not contain. GHRP-6, the older peptide with the near-identical name, begins His-D-Trp instead and shares the remaining four residues and the amide. Those two substitutions separate the peptides clearly by mass. GHRP-2 has a theoretical mass of 818.0 Da and GHRP-6 873.0 Da, so the LC-MS identity result on the certificate shows which of the two is in the vial. The same figure puts 10 mg of GHRP-2 at about 12.2 µmol, a little less in practice because the powder also holds the residual water the certificate reports.

What the research covers

Where GHRP-2 came from

GHRP-2 belongs to a series of small growth hormone-releasing peptides synthesised by Cyril Bowers' group at Tulane University and developed with the German company Polygen¹. An earlier peptide from the same laboratory, GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2), was studied by Bowers and colleagues in 18 healthy men in 1990: it was a potent releaser of growth hormone, and at submaximal amounts it acted synergistically with growth hormone-releasing hormone (GHRH)². GHRP-2 keeps the last four residues of that peptide and replaces the first two. When these peptides were made, nobody knew which receptor they acted on. Howard and colleagues cloned it in 1996, a G protein-coupled receptor in the pituitary and hypothalamus of pigs and humans, and showed that it was the target of the growth hormone secretagogues³. A 2004 drug profile describes pralmorelin as mimicking the actions of ghrelin, a 28-residue octanoylated peptide that regulates growth hormone release¹.

Use as a test of growth hormone reserve

The clinical interest in pralmorelin was diagnostic. The same profile reports that it raises plasma growth hormone sharply in healthy subjects regardless of sex, obesity or age, while the response in growth hormone deficiency is much smaller¹. A receiver-operating-characteristic analysis set a growth hormone peak of 15.0 µg/L as the threshold separating deficient from normal secretion, and Kaken acquired worldwide manufacturing and marketing rights¹. A 2010 doping-control paper described GHRP-2 as in use for diagnosing growth hormone deficiency⁴.

Pharmacokinetics and appetite in human studies

Pihoker and colleagues ran a phase I study in ten prepubertal children with short stature, measuring GHRP-2 and growth hormone in blood over two hours after a single exposure⁵. Plasma GHRP-2 fell in two phases, and the terminal half-life averaged 0.55 hours⁵. GHRP-2 also affects eating, as ghrelin does. In seven lean, healthy men, GHRP-2 compared with saline increased the amount eaten at a buffet meal by 35.9%, every subject ate more, the mix of fat, protein and carbohydrate did not change, and growth hormone rose as expected⁶. The authors proposed GHRP-2 as a tool for studying how ghrelin acts on eating in humans⁶.

Detection and metabolism

Growth hormone secretagogues are prohibited in sport by the World Anti-Doping Agency, and Okano and colleagues developed a liquid chromatography and tandem mass spectrometry method to find GHRP-2 in urine⁴. Alongside the intact peptide the method targets a metabolite, D-Ala-D-2-Nal-Ala-OH, which is the first three residues of the chain ending in a free acid; in ten male volunteers both were detected in every case⁴.

What is not established

The human evidence for GHRP-2 rests on small, short studies: ten children in the pharmacokinetic work⁵ and seven men in the food intake study⁶. Several findings often quoted for the whole class were measured with GHRP-6. In the 1990 study, prolactin and cortisol roughly doubled only at the highest amount of GHRP-6 tested, while LH and TSH did not change², and none of the abstracts cited here reports the same hormone panel for GHRP-2. None of these studies used SCALE Performance material, and the vial sold here is not Kaken's diagnostic product. The GHRP-2 vs GHRP-6 guide sets the two peptides side by side.

Frequently asked questions

References

1. . Pralmorelin: GHRP 2, GPA 748, growth hormone-releasing peptide 2, KP-102 D, KP-102 LN, KP-102D, KP-102LN. Drugs R D. 2004;5(4):236-9. DOI · PubMed
2. Bowers CY, Reynolds GA, Durham D, et al. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. J Clin Endocrinol Metab. 1990;70(4):975-82. DOI · PubMed
3. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-7. DOI · PubMed
4. Okano M, Sato M, Ikekita A, et al. Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom. 2010;24(14):2046-56. DOI · PubMed
5. Pihoker C, Kearns GL, French D, et al. Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children. J Clin Endocrinol Metab. 1998;83(4):1168-72. DOI · PubMed
6. Laferrère B, Abraham C, Russell CD, et al. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men. J Clin Endocrinol Metab. 2005;90(2):611-4. DOI · PubMed