GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Activation of growth hormone secretagogue receptor induces time-dependent clock phase delay in mice.
Zhou. Lan L; Gao. Qian Q; Zhang. Peng P; Guo. Shu S; Gu. Jingli J; Hao. Wei W; Cao. Ji-Min JM
Key Findings
- A single dose of GHRP‑6 (100 µg/kg) given at CT12 caused a measurable phase‑delay in the mice’s circadian activity rhythm, but the same dose at other times did not.
- The phase‑delay was eliminated by a GHS‑receptor antagonist, a CaMKII inhibitor (KN‑93), or an anti‑pCREB antibody, showing the pathway involved.
- GHRP‑6 at CT12 increased calcium signals and neuronal firing in the SCN, lowered glutamate and GABA levels, and altered expression of clock genes (Per1, Bmal1, etc.), mirroring the early‑night light‑induced delay.
Practical Outcomes
- For biohackers, the study suggests that the timing of GHRP‑6 administration could influence sleep‑wake timing, potentially serving as a tool to shift the circadian clock if given at the right night‑time window. However, the data are from mice, not humans, and the effect depends on precise timing and dose, so any real‑world protocol would be experimental and should be approached with caution.
Summary
In mice, giving the peptide GHRP‑6 at the start of the night (the early dark phase) pushes the internal clock later, making the animals’ activity rhythm shift backward. This effect only happens at that specific time, relies on the GHRP‑6 receptor, calcium signaling, and changes in clock‑gene activity, and can be blocked by a receptor antagonist or inhibitors of the signaling pathway.
Abstract
Early studies have reported a phase-shifting effect of growth hormone secretagogues (GHSs). This study aimed to determine the mechanism of action of GHSs. We examined the response of the hypothalamic suprachiasmatic nuclei (SCN) to growth hormone releasing peptide-6 (GHRP-6) by assessing effects on the phase of locomotor activity rhythms, SCN neuronal discharges, and the potential signaling pathways involved in the drug action on circadian rhythms. The results showed that bolus administration of GHRP-6 (100 μg/kg ip) at the beginning of subjective night (CT12) induced a phase delay of the free-running rhythms in male C57BL/6J mice under constant darkness, but did not elicit phase shift at other checked circadian time (CT) points. The phase-delay effect of GHRP-6 was abolished by d-(+)-Lys-GHRP-6 (GHS receptor antagonist), KN-93 [calcium/calmodulin-dependent protein kinase II (CaMK) II inhibitor], or anti-phosphorylated (p)-cAMP response element-binding protein (CREB) antibody. Further analyses demonstrated that GHRP-6 at CT12 induced higher calcium mobilization and neuronal discharge in the SCN compared with that at CT6, decreased the levels of glutamate and γ-aminobutyric acid, increased the levels of p-CaMKII, p-CREB, and period 1, and delayed the circadian expressions of circadian locomotor output cycles kaput, Bmal1, and prokineticin 2 in the SCN; these signaling changes resulted in behavioral phase delay. Collectively, GHRP-6 induces a CT-dependent phase delay via activating GHS receptor and the downstream signaling, which is partially similar to the signaling cascade of light-induced phase delay at early night. These novel observations may help to better understand the role of GHSs in circadian physiology.
Study Information
pubmed
2014
2014-07-29T00:00:00.000Z
10.1152/ajpendo.00535.2013
8
54