GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Binding of a growth hormone releasing hexapeptide to specific hypothalamic and pituitary binding sites.
Codd. E E EE; Shu. A Y AY; Walker. R F RF
Key Findings
- GHRP‑6 binds reversibly and saturably to membrane fragments from both hypothalamus and anterior pituitary.
- Two distinct binding components were identified: a high‑affinity site (Kd ≈ 10⁻⁸ M) and a low‑affinity site (Kd ≈ 10⁻⁵ M).
- Across related peptide variants, the strength of binding to these sites correlates significantly with their ability to stimulate growth‑hormone release.
Practical Outcomes
- For biohackers, this confirms that GHRP‑6’s GH‑boosting effect is mediated by specific receptors, so dosing strategies should aim for plasma levels that reach the high‑affinity (nanomolar) range. It also suggests that small changes to the peptide’s structure can alter its binding and effectiveness, guiding the choice of analogues or dosing schedules.
Summary
The study shows that the growth‑hormone‑releasing hexapeptide (GHRP‑6) sticks to two kinds of binding spots in the brain’s hypothalamus and the pituitary gland. One spot grabs the peptide very tightly (nanomolar range) and the other less tightly (micromolar range). The stronger the binding, the more growth hormone gets released, confirming that these sites are part of how GHRP‑6 works.
Abstract
The drug SK&F 110679 (His-D-Trp-Ala-Trp-D-Phe-LysNH2), is an enkephalin-derived hexapeptide, which specifically releases growth hormone in a wide variety of species in vivo and in vitro. Previous binding studies, using ligands which are specific for mu and delta opioid binding sites, demonstrated an inverse relationship between the opioid binding potency and the potency in releasing growth hormone of a series of peptides related to SK&F 110679. In an attempt to understand its mode of action better, a binding assay for the peptide was established using a ligand which had been tritium labelled at the D-Trp2 residue. Membrane fragments from both the hypothalamus and anterior pituitary tissue were found to contain sites to which [3H]SK&F 110679 reversibly and saturably bound. The binding curves for [3H]SK&F 110679 to membrane fragments of both hypothalamus and anterior pituitary were resolved into two binding components with the computer program LIGAND. The Kd's obtained were in the 10(-8) M and 10(-5) M range. The relationship of these binding sites to the growth hormone-releasing activity of the peptide was explored by examining the relationship between the binding and potency in releasing growth hormone of a series of peptides related to SK&F 110679. For sites in both the hypothalamus and pituitary, a significant correlation between binding and the release of growth hormone was obtained. Thus, these binding sites appeared to be involved in the release of growth hormone by SK&F 110679-related peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
Study Information
pubmed
1989
1989-10-01T00:00:00.000Z
10.1016/0028-3908(89)90129-9
162
10