GHRP-2, a GHS-R agonist, directly acts on myocytes to attenuate the dexamethasone-induced expressions of muscle-specific ubiquitin ligases, Atrogin-1 and MuRF1.
Yamamoto. Daisuke D; Ikeshita. Nobuko N; Matsubara. Takako T; Tasaki. Hiromitsu H; Herningtyas. Elizabeth Henny EH; Toda. Keizo K; Iida. Keiji K; Takahashi. Yutaka Y; Kaji. Hidesuke H; Chihara. Kazuo K; Okimura. Yasuhiko Y
Key Findings
- GHRP‑2 reduced dexamethasone‑induced Atrogin‑1 mRNA in rat soleus muscle.
- GHRP‑2 lowered MuRF1 mRNA both in the presence and absence of dexamethasone.
- The anti‑atrophy effect was blocked by a ghrelin‑receptor antagonist, confirming it works through GHS‑R1a.
- GHRP‑2 did not alter plasma or muscle IGF‑I levels, indicating a mechanism independent of IGF‑I.
Practical Outcomes
- For biohackers, this suggests GHRP‑2 might help blunt muscle loss during periods of high cortisol (e.g., intense training, stress, or short‑term steroid use). However, the data are from rats and cell cultures, so human dosing, safety, and real‑world efficacy remain unknown. If experimenting, consider low‑dose protocols and monitor muscle markers, but treat this as a promising hypothesis rather than a proven regimen.
Summary
The study shows that GHRP‑2, a peptide that activates the ghrelin receptor, can directly lower the muscle‑wasting signals Atrogin‑1 and MuRF1 in rat muscle and cultured muscle cells, even when those cells are exposed to the catabolic hormone dexamethasone. This effect happens without changing IGF‑1 levels, suggesting a direct protective action on muscle fibers.
Abstract
Recent reports suggest that Atrogin-1 and MuRF1, E3 ubiquitin ligases, play a pivotal role in muscle atrophy. In the present study, effect of Growth Hormone Releasing Peptide-2 (GHRP-2), a GH secretagogue receptor (GHS-R) agonist, on the expressions of Atrogin-1 and MuRF1 in vivo rat muscles was examined. Dexamethasone administration increased Atrogin-1 mRNA level in rat soleus muscle. The increased mRNA level of Atrogin-1 was significantly attenuated by GHRP-2. In addition, GHRP-2 decreased MuRF1 mRNA level irrespective of the presence of dexamethasone. Although IGF-I is a well-known protective factor for muscle atrophy, GHRP-2 did not influence plasma IGF-I levels and IGF-I mRNA levels in muscles. To clarify a direct effect of GHRP-2, differentiated C2C12 myocytes were used. Ten micrometer dexamethasone increased both Atrogin-1 and MuRF1 mRNA levels in C2C12 cells. GHRP-2 attenuated dexamethasone-induced expression of them dose-dependently and decreased the basal level of MuRF1 mRNA. The suppressive effect on the expressions of Atrogin-1 and MuRF1 by GHRP-2 was blocked by [D-Lys(3)]-GHRP-6, a GHS-R1a blocker, suggesting the effect of GHRP-2 was mediated through GHS-R1a. Taken together, GHRP-2 directly attenuates Atrogin-1 and MuRF1 mRNA levels through ghrelin receptors in myocytes.
Study Information
pubmed
2007
2007-12-05T00:00:00.000Z
10.1016/j.lfs.2007.11.019
29
37