Determinants of GH-releasing hormone and GH-releasing peptide synergy in men

Summary

Human physiology study of what shapes the synergistic GH response when GHRH and a GH-releasing peptide (GHRP-2) are infused together. It used neither CJC-1295 nor ipamorelin. It is relevant to that pairing only at the class level: CJC-1295 is a GHRH analog and ipamorelin is a GH-releasing peptide. The authors start from the point that GHRH-GHRP synergy markedly stimulates pulsatile GH secretion. They asked how age, sex steroids and abdominal-visceral fat modify that synergy.

Key Findings

• GHRH-GHRP synergy correlated negatively with age and abdominal visceral fat (both P < 0.001) and positively with IGF-I (P < 0.001) and IGFBP-3 (P = 0.031)
• Abdominal visceral fat, IGF-I and IGFBP-3 together explained 60% of the variability in GHRH-GHRP synergy (P < 0.001)
• Basal (non-pulsatile) GH secretion correlated positively with testosterone and estradiol; estradiol explained 17% of its variability
• Fasting pulsatile GH secretion fell with age and rose with IGF-I and IGFBP-3; IGF-I explained 20% of its variability
• The authors conclude that basal, pulsatile and synergistic peptide-driven GH secretion are each selectively controlled by visceral fat, estradiol and IGF-I in healthy men

Methodology

47 healthy men aged 18-74 years. The gonadal axis was downregulated with leuprolide, then placebo or testosterone was added back to clamp sex-steroid levels. GHRH and GHRP-2 were infused simultaneously to evoke synergy. Stepwise forward-selection multivariate analysis related synergy, basal GH and pulsatile GH to age, sex steroids, IGF-I, IGFBP-3 and abdominal visceral fat.

Limitations

• Men only
• Used GHRH and GHRP-2 by infusion, not CJC-1295 or ipamorelin by subcutaneous injection
• The abstract does not report GH responses to either peptide alone, so it does not itself quantify how much larger the combined response is
• Acute hormone-response study; no body composition or clinical outcomes
• The synergy findings are correlations across participants

Relevance to Content

Supports the general premise behind CJC-1295 + ipamorelin stacks, that GHRH-type and GHRP-type peptides act synergistically on GH secretion, at the level of the peptide classes rather than these two drugs. It also suggests the synergy is weaker in older men and in men with more visceral fat. It does not test the stack itself.

See Also

• Parent compound: CJC-1295
• Ipamorelin