The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3',5'-monophosphate accumulation in rat primary pituitary cell culture.
Cheng. K K; Chan. W W WW; Barreto. A A; Convey. E M EM; Smith. R G RG
Key Findings
- GHRP‑6 stimulates GH release in a dose‑dependent way, with half‑maximal effect at ~7 nM and maximal at 100 nM.
- When combined with GRF, GHRP‑6 produces a synergistic increase in GH release and amplifies GRF‑induced cAMP signaling.
- Prolonged exposure to GHRP‑6 reduces baseline GH release and causes temporary desensitisation, which fully recovers after ~1 hour without the peptide.
Practical Outcomes
- For biohackers, using GHRP‑6 at low nanomolar doses can quickly raise GH levels, especially if paired with a GRF analogue like CJC‑1295 for a stronger effect. Avoid continuous, high‑dose exposure to prevent short‑term desensitisation; cycling (e.g., a few hours on, then a break) can maintain responsiveness. The synergy suggests combined protocols may be more effective than either peptide alone.
Summary
The study shows that the peptide GHRP‑6 (also called GRF‑1‑29) can boost growth hormone release from pituitary cells, especially when used together with a growth‑hormone‑releasing factor (GRF). The effect happens quickly (within 15 minutes) and peaks at very low concentrations. If you use GHRP‑6 for a long time, the cells become less responsive, but this desensitisation goes away after about an hour without the peptide.
Abstract
His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) stimulated GH release from rat primary pituitary cells in a time- and dose-dependent manner. Stimulation was observed after a 15-min, but not a 4-h, incubation. The concentrations of GHRP-6 required for half-maximal and maximal stimulation were 7 x 10(-9) and 10(-7) M, respectively. GH release induced by GHRP-6 was not affected by the addition of either naloxone or the GRF antagonist [N-Ac-Tyr1,D-Arg2]GRF-(1-29)-NH2. The latter inhibited GRF-stimulated GH release by shifting the dose-response curve to the right. His-D-Trp-D-Lys-Trp-D-Phe-Lys-NH2, an analog of GHRP-6, inhibited GH release stimulated by GHRP-6 without affecting that induced by GRF. When present together at maximal concentrations, GHRP-6 and GRF produced a synergistic effect on GH release. GHRP-6 had no effect on intracellular cAMP levels, whereas GRF increased intracellular cAMP concentrations by 3-fold. Combined treatment of pituitary cells with GRF and GHRP-6 resulted in a potentiation of the GRF-induced increase in cAMP levels. Basal GH release was reduced by 30% after pretreatment with GHRP-6 (10(-7) M) for 1 h. Pretreatment with GHRP-6 also decreased the subsequent response to GHRP-6, but not GRF. In contrast, pretreatment with GRF for 1 h had no effect on the subsequent action of GHRP-6 or GRF on GH release. The desensitization induced by GHRP-6 was completely reversed within 1 h after removal of the peptide. Results from this study indicate that GHRP-6 and GRF stimulated GH release from somatotrophs via different receptors and through discrete mechanisms.
Study Information
pubmed
1989
10.1210/endo-124-6-2791