GHRP-6

GHRP-6 is the synthetic hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, which Cyril Bowers and colleagues described in 1984 as releasing growth hormone from the pituitary without releasing LH, FSH, TSH or prolactin. This listing is the 10 mg vial of freeze-dried powder, the main fill of the range, and a 5 mg vial is also sold. Its literature runs from pituitary and animal work through the first human studies to the cloning of its receptor and the discovery of ghrelin, the receptor's natural ligand.

Handling notes: two tryptophans

Two of GHRP-6's six residues carry an indole ring: D-tryptophan at position 2 and tryptophan at position 4. Tryptophan is among the residues that undergo primary photo-oxidation in proteins, along with tyrosine, phenylalanine and cysteine, and a review of light damage in protein products links photodegradation to structural changes that could alter stability and activity¹. Counting the D-phenylalanine, GHRP-6 has three of those residues in six positions, so the instruction to keep it dark applies to a solution as much as to the powder.

The same rings give a simple optical handle. Pace and colleagues' equation predicts absorbance at 280 nm from the numbers of tryptophan, tyrosine and cystine residues, with tryptophan contributing the most per residue². GHRP-6 has no tyrosine or cystine, so its 280 nm absorbance comes from the two indoles, which makes UV absorbance a practical way to estimate the concentration of a solution. The equation was fitted to folded proteins, so for a hexapeptide it gives an estimate rather than an exact value.

What the research covers

Discovery and specificity

Bowers and colleagues reported GHRP-6 in 1984 under the name [His1,Lys6]GHRP³. In pituitary incubations and in live animals it released growth hormone in a graded way without releasing LH, FSH, TSH or prolactin, and in limited tests it did not release insulin or glucagon either³. It was active in rats, monkeys, lambs and calves, which the authors read as a lack of species dependence³. In rats growth hormone rose within minutes and peaked at 10 to 20 minutes, the response lasted longer than that of the larger releasing factors GHRF-44 and GHRF-40, and both forms of somatostatin blocked it, with SRIF-28 about four times as active as SRIF-14 in vitro³.

First human data

The first human study, published by Ilson and colleagues in 1989, enrolled 17 healthy men, with saline as the control in eight⁴. Growth hormone rose consistently above a threshold amount and in proportion to the amount used, while LH, FSH, TSH and ACTH did not change, and the peptide was well tolerated⁴. Pharmacokinetic data came much later. In 2013 Cabrales and colleagues measured GHRP-6 in the plasma of nine healthy men with a validated LC-MS method⁵. Its disposition fitted a two-compartment model with a distribution half-life of 7.6 minutes and an elimination half-life of 2.5 hours, and exposure rose roughly in proportion to the amount⁵. The authors also describe GHRP-6 as supporting tissue viability in several organs, though the abstract does not present that evidence⁵.

The receptor and ghrelin

For twelve years GHRP-6 acted through a receptor nobody had identified. In 1996 Howard and colleagues cloned a G protein-coupled receptor from the pituitary and hypothalamus of pigs and humans, showed that it was the target of the growth hormone secretagogues, and argued that these synthetic compounds mimic a hormone not yet discovered⁶. That hormone turned up in 1999, when Kojima and colleagues purified a 28-residue peptide from rat stomach, with an n-octanoyl group on serine 3 that is required for activity, and named it ghrelin⁷. In rats, ghrelin stimulated feeding as well as growth hormone release, with a rapid onset, and in one set of experiments it also raised ACTH and lowered TSH⁸.

What is not established

GHRP-6 is often described as the most appetite-stimulating peptide of its class, yet none of the abstracts cited here measured food intake after GHRP-6. The feeding data are for ghrelin in rats⁸, and carrying them over to GHRP-6 depends on the shared receptor. The human studies cited measured short-term responses in small groups of healthy men, so they say little about repeated or long-term exposure. None of these studies used SCALE Performance material. The GHRP-2 vs GHRP-6 guide sets the two peptides side by side.

Frequently asked questions

References

1. Kerwin BA, Remmele RL Jr. Protect from light: photodegradation and protein biologics. J Pharm Sci. 2007;96(6):1468-79. DOI · PubMed
2. Pace CN, Vajdos F, Fee L, et al. How to measure and predict the molar absorption coefficient of a protein. Protein Sci. 1995;4(11):2411-23. DOI · PubMed
3. Bowers CY, Momany FA, Reynolds GA, et al. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology. 1984;114(5):1537-45. DOI · PubMed
4. Ilson BE, Jorkasky DK, Curnow RT, et al. Effect of a new synthetic hexapeptide to selectively stimulate growth hormone release in healthy human subjects. J Clin Endocrinol Metab. 1989;69(1):212-4. DOI · PubMed
5. Cabrales A, Gil J, Fernández E, et al. Pharmacokinetic study of Growth Hormone-Releasing Peptide 6 (GHRP-6) in nine male healthy volunteers. Eur J Pharm Sci. 2013;48(1-2):40-6. DOI · PubMed
6. 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
7. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656-60. DOI · PubMed
8. Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141(11):4325-8. DOI · PubMed