Ghrelin
Endogenous 28-amino-acid orexigenic peptide produced by gastric oxyntic cells — the natural ligand for the GHS-R1a receptor. Studied for cachexia, post-surgery gastroparesis, and GH deficiency.
🔬 Mechanism of Action
Ghrelin is the only known orexigenic (appetite-stimulating) peptide hormone in humans. It is a 28-amino-acid peptide with a unique octanoyl modification on Ser-3 (essential for GHS-R1a binding). Produced primarily by X/A-like cells in gastric oxyntic mucosa, ghrelin circulates and binds the growth hormone secretagogue receptor (GHS-R1a) on hypothalamic NPY/AgRP neurons, stimulating appetite. Simultaneously, it acts on anterior pituitary somatotrophs to release GH. Ghrelin levels rise pre-prandially and fall post-prandially, functioning as a "hunger signal." Beyond appetite and GH, ghrelin exerts cardioprotective effects (reducing infarct size in animal MI models), anti-inflammatory actions via vagal afferent activation, and improves gastric motility.
Source: PMID: 10604470
📜Background & History
Ghrelin was discovered in 1999 by Masayasu Kojima and colleagues in rat stomach. It was the first known endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a), explaining how synthetic secretagogues like GHRP-6 worked. Ghrelin is now recognized as a key regulator of energy homeostasis, connecting gut-brain signaling for appetite, metabolism, and growth hormone release. Its role in cachexia (cancer-related wasting) has driven clinical trials.
🎯 Research Use Cases
- ✓Cancer cachexia research
- ✓Gastroparesis
- ✓GH deficiency research
- ✓Anorexia nervosa research
- ✓Post-surgical ileus
💉 Dosing Protocol
| Typical Dose | 1-5 mcg/kg IV (research) |
| Frequency | Per study protocol |
| Half-Life | 0.5 hours |
| Common Vial Sizes | 5 mg |
🧪 Reconstitution Example
⚠️Safety & Considerations
Clinical use limited by very short half-life (~30 min). May cause transient hyperglycemia via GH-mediated insulin resistance. Potential concern for stimulating appetite in conditions where weight gain is contraindicated.
⚡Interactions & Contraindications
May increase appetite and food intake. Can cause transient hyperglycemia. Interacts with insulin and leptin signaling pathways. Ghrelin O-acyltransferase (GOAT) inhibitors are being developed as anti-obesity agents.
🔗Synergies & Common Stacks
GHRP-2 is a synthetic ghrelin receptor agonist — ghrelin is the endogenous ligand. They activate the same receptor but ghrelin has additional metabolic effects.
MK-677 is a non-peptide oral ghrelin mimetic. It provides sustained oral GHS-R1a activation that compensates for ghrelin's extremely short half-life.