The effects of GH-releasing peptide-6 (GHRP-6) and GHRP-2 on intracellular adenosine 3',5'-monophosphate (cAMP) levels and GH secretion in ovine and rat somatotrophs.
Wu. D D; Chen. C C; Zhang. J J; Bowers. C Y CY; Clarke. I J IJ
Key Findings
- GHRP‑2 increases intracellular cAMP and GH release, similar to GHRF.
- GHRP‑6 releases GH without raising cAMP, but its effect is still calcium‑dependent.
- Combining GHRP‑2 or GHRP‑6 with GHRF produces additive GH release, implying different receptor pathways.
- Species differences observed: GHRP‑2 raises cAMP in sheep but not rat cells; GHRP‑6 boosts cAMP only in rat cells when paired with GHRF.
Practical Outcomes
- For biohackers, the data suggest that stacking GHRP‑6 with a GHRF peptide could enhance GH spikes more than either alone, and that calcium availability matters for the effect. However, because the work is in animal pituitary cells, human dosing and safety remain uncertain, so start with low doses and monitor hormone levels.
Summary
The study shows that two growth‑hormone‑releasing peptides work differently: GHRP‑2 raises cAMP inside pituitary cells like the natural hormone GHRF, while GHRP‑6 triggers GH release without raising cAMP. Both can add to each other's effects, suggesting they hit separate receptors, and all need calcium entry to work. Results differ between sheep and rat cells, hinting that human responses might vary too.
Abstract
The mechanism of action of GH-releasing peptide-6 (GHRP-6) and GHRP-2 on GH release was investigated in ovine and rat pituitary cells in vitro. In partially purified sheep somatotrophs, GHRP-2 and GH-releasing factor (GRF) increased intracellular cyclic AMP (cAMP) concentrations and caused GH release in a dose-dependent manner; GHRP-6 did not increase cAMP levels. An additive effect of maximal doses of GRF and GHRP-2 was observed in both cAMP and GH levels whereas combined GHRP-6 and GHRP-2 at maximal doses produced an additive effect on GH release only. Pretreatment of the cells with MDL 12,330A, an adenylyl cyclase inhibitor, prevented cAMP accumulation and the subsequent release of GH that was caused by either GHRP-2 or GRF. The cAMP antagonist, Rp-cAMP also blocked GH release in response to GHRP-2 and GRF. The cAMP antagonist did not prevent the effect of GHRP-6 on GH secretion whereas MDL 12,330A partially reduced the effect. An antagonist for the GRF receptor, [Ac-Tyr1,D-Arg2]-GRF 1-29, significantly diminished the effect of GHRP-2 and GRF on cAMP accumulation and GH release, but did not affect GH release induced by GHRP-6. Somatostatin prevented cAMP accumulation and GH release responses to GHRP-2, GRF and GHRP-6. Ca2+ channel blockade did not affect the cAMP increase in response to GHRP-2 or GRF but totally prevented GH release in response to GHRP-2, GRF and GHRP-6. These results indicated that GHRP-2 acts on ovine pituitary somatotrophs to increase cAMP concentration in a manner similar to that of GRF; this occurs even during the blockade of Ca2+ influx. GHRP-6 caused GH release without an increase in intracellular cAMP levels. GH release in response to all three secretagogues was reduced by somatostatin and was dependent upon the influx of extracellular Ca2+. The additive effect of GHRP-2 and GRF or GHRP-6 suggested that the three peptides may act on different receptors. In rat pituitary cell cultures, GHRP-6 had no effect on cAMP levels, but potentiated the effect of GRF on cAMP accumulation. The synergistic effect of GRF and GHRP-6 on cAMP accumulation did not occur in sheep somatotrophs. Whereas GHRP-2 caused cAMP accumulation in sheep somatotrophs, it did not do so in rat pituitary cells. These data indicate species differences in the response of pituitary somatotrophs to the GHRPs and this is probably due to different subtypes of GHRP receptor in rat or sheep.
Study Information
pubmed
1996
10.1677/joe.0.1480197