Hexarelin: A Research Review

Abstract

Hexarelin is a synthetic growth hormone secretagogue (GHS) and peptide analogue of GHRP-6. It acts via the ghrelin receptor (GHS-R1a) to stimulate pulsatile secretion of growth hormone (GH). Compared with endogenous ghrelin and earlier GHS molecules, Hexarelin has shown high potency and reproducibility in eliciting GH release. Research has explored its potential applications in endocrinology, cardiology, and tissue repair. This paper summarizes mechanisms, experimental dosing regimens, and findings from preclinical and early human studies.

1. Introduction

Growth hormone secretagogues (GHS) represent a class of synthetic peptides and small molecules that act through the ghrelin receptor (GHS-R1a) to stimulate GH release from pituitary somatotrophs. Hexarelin (His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH₂) is a hexapeptide analogue derived from GHRP-6 with enhanced stability and GH-releasing activity.

2. Mechanism of Action

• Receptor target: Binds to the growth hormone secretagogue receptor (GHS-R1a), the same receptor as endogenous ghrelin.
• GH release: Increases both basal and pulsatile secretion of GH from the anterior pituitary.
• Endocrine effects: GH rise leads to increases in IGF-1, which mediates anabolic and metabolic actions.
• Cardioprotective signaling: Preclinical research suggests Hexarelin interacts with cardiac receptors independent of GH, offering possible protective effects on myocardium.

3. Research Findings

3.1 Endocrinology & GH axis

• Potent GH release: Human studies show Hexarelin reliably increases GH levels in both young and elderly subjects.
• Desensitization: Repeated administration may lead to partial tachyphylaxis (reduced GH response over time).

3.2 Cardiovascular research

• Cardioprotection: Animal models demonstrate cardioprotective effects, including improved ventricular function, reduced apoptosis, and enhanced repair after ischemic injury.
• Independent of GH: Some effects appear GH/IGF-1 independent, suggesting a direct cardiac receptor-mediated pathway.

3.3 Musculoskeletal & metabolism

• Muscle and bone: Increased anabolic signaling through GH/IGF-1 axis suggests potential applications in muscle wasting and osteoporosis research.
• Lipid metabolism: Some studies indicate reductions in fat mass and improvements in metabolic parameters in preclinical models.

3.4 Neuroendocrine research

• Investigated for its effects on appetite, neuroprotection, and hypothalamic–pituitary function.

4. Typical Experimental Dosing

⚠️ Note: The following are research-only dosing ranges reported in preclinical and early clinical studies. Not for clinical or human use outside controlled research.

• Animal studies:
  • Typical range: 10–100 μg/kg/day (mice, rats, dogs) via injection.
• Human studies:
  • Single subcutaneous injection: 1–2 μg/kg → rapid GH peak within ~30 minutes.
  • Repeated dosing: 2–3 μg/kg SC once or twice daily has been tested in short-term trials, showing increased GH/IGF-1 but partial desensitization over weeks.
  • Absolute doses reported: ~100–200 μg per injection in adult volunteers.

5. Safety & Limitations

• Adverse effects (reported in studies): injection site irritation, transient flushing, mild prolactin or cortisol elevation (less than older GHS analogues).
• Desensitization: Diminished GH response with chronic administration — a key limitation.
• Cardiac effects: Preclinical cardioprotection appears beneficial, but human clinical translation remains unproven.
• Regulatory status: Not FDA-approved; considered an investigational peptide.

6. Conclusion

Hexarelin is a potent growth hormone secretagogue with dual interest in both endocrinology and cardiology research. It reliably increases GH and IGF-1 in humans and has demonstrated cardioprotective effects in animal models. However, issues of desensitization and limited long-term safety data restrict clinical applicability. Its primary value remains as a research tool for studying the GH/IGF-1 axis and cardiac receptor biology.

7. References (sample)

1. Bowers CY. (1998). Growth hormone-releasing peptides: animal and human studies. Endocr Rev.
2. Broglio F, et al. (1999). Hexarelin, a growth hormone secretagogue, in humans: endocrine and metabolic effects. J Clin Endocrinol Metab.
3. Locatelli V, et al. (2002). Hexarelin and cardiovascular function. Ann N Y Acad Sci.
4. Muccioli G, et al. (2001). Hexarelin and the GH secretagogue receptor: cardiac actions. Cardiovasc Res.

⚠️ Disclaimer: Hexarelin remains experimental. All dosing information provided is from preclinical and limited human studies. It is not approved for therapeutic use and should only be used in controlled research.