GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Stimulation of growth hormone release from rat primary pituitary cells by L-692,429, a novel non-peptidyl GH secretagogue.
Cheng. K K; Chan. W W WW; Butler. B B; Wei. L L; Schoen. W R WR; Wyvratt. M J MJ; Fisher. M H MH; Smith. R G RG
Key Findings
- L‑692,429 stimulates GH release with an EC50 of ~60 nM, while GHRP‑6 is more potent (EC50 ~10 nM) and GRF is even stronger (EC50 ~0.5 nM).
- Both L‑692,429 and GHRP‑6 do not change intracellular cAMP levels alone, but they synergize with GRF to raise cAMP and GH output.
- Maximum GH release from GHRP‑6 or L‑692,429 cannot be increased by adding the other, indicating a shared pathway.
- Somatostatin at 20 nM completely blocks the GH‑releasing effect of L‑692,429.
Practical Outcomes
- For biohackers using GHRP‑6, pairing it with a GHRH peptide (like GRF) can produce a stronger GH surge than GHRP‑6 alone. Timing doses away from periods of high somatostatin (e.g., after meals) may help preserve the GH‑boosting effect. The study confirms that GHRP‑6 works via a mechanism similar to non‑peptide secretagogues, reinforcing the rationale for the common GHRP‑6 + GRF “stack.”
Summary
The study shows that a new non‑peptide compound, L‑692,429, can trigger growth hormone (GH) release from rat pituitary cells just like the popular peptide GHRP‑6. Both work best at very low concentrations, don’t raise cAMP on their own, but become more powerful when paired with a growth‑hormone‑releasing factor (GRF). Adding both GHRP‑6 and L‑692,429 together doesn’t boost GH any further, and the effect can be completely blocked by somatostatin.
Abstract
L-692,429, a benzolactam derivative, stimulated GH release from rat primary pituitary cells in a dose-dependent manner. The concentration of L-692,429 required for half-maximal stimulation were 59.6 +/- 7.3 nM. Under the same conditions, GHRP-6 and GRF had EC50 values of 10.3 +/- 1.9 nM and 0.47 +/- 0.09 nM, respectively. L-692,428, the enantiomer of L-692,429, was inactive at a concentration as high as 2 microM. Like GHRP-6, L-692,429 had no effect on intracellular cAMP level; however, it synergized with GRF to further increase not only the accumulation of cAMP but also the release of GH. The magnitude of GH release stimulated by maximal concentrations of L-692,429 and GHRP-6 was comparable. Interestingly, when presented together in maximal concentrations, L-692,429 and GHRP-6 did not cause additional GH release when compared with either secretagogue alone. The L-692,429-stimulated GH release was completely inhibited by 20 nM somatostatin. To our knowledge, L-692,429 is the first non-peptidyl GH secretagogue which has a direct effect on the release of growth hormone from rat primary pituitary cells. Its effect is most likely mediated through a mechanism which is similar to that of GHRP-6.
Study Information
pubmed
1993
10.1210/endo.132.6.8389289