PMID-15788704 – Ghrelin Structure and Function Review
van der Lely AJ, Tschop M, Heiman ML, Ghigo E. "Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin," Endocr Rev, 2004;25(3):426-457.
Quick Reference
| Property | Value |
|---|---|
| PMID | 15788704 |
| DOI | 10.1210/er.2002-0029 |
| Year | 2004 |
| Journal | Endocrine Reviews |
| Study Type | Narrative Review |
| Evidence Level | V |
| Sample | N/A (review) |
| Peptide(s) Studied | Ghrelin |
Key Findings
- Comprehensive characterization of ghrelin as a 28-amino acid peptide with unique octanoyl modification at Ser3
- Ghrelin gene (GHRL) encodes preproghrelin (117 aa) which is processed to ghrelin (28 aa) and obestatin (23 aa)
- GHS-R exists in two splice variants: GHS-R1a (functional, 7-TM GPCR) and GHS-R1b (truncated, 5-TM, non-signaling)
- Ghrelin is the most potent endogenous stimulus for GH secretion (more potent than GHRH on a molar basis)
- Dual GH-releasing pathway: ghrelin acts synergistically with GHRH (ghrelin via GHS-R1a, GHRH via GHRH-R); this explains why CJC-1295 + ipamorelin is more effective than either alone
- Ghrelin's orexigenic effect is mediated via arcuate nucleus NPY/AgRP neurons (independent of GH release)
- Ghrelin stimulates gastric motility and acid secretion via vagal afferents
- Ghrelin has direct cardiovascular effects: reduces systemic vascular resistance, increases cardiac output
- In pathological states: elevated in anorexia nervosa, Prader-Willi syndrome; reduced after bariatric surgery
Study Design
Exhaustive narrative review in Endocrine Reviews covering molecular biology, receptor pharmacology, physiological functions across organ systems, pathophysiology in disease states, and pharmacological applications of ghrelin and ghrelin mimetics.
Limitations
- Published 2004; predates discovery of GOAT enzyme (2008) and many therapeutic applications
- Does not cover more recently identified ghrelin functions (bone metabolism, immune modulation in detail)
- Some proposed therapeutic applications remain unvalidated
Clinical Relevance
This Endocrine Reviews article remains one of the most comprehensive references on ghrelin biology. Its most important clinical insight for the vault is the mechanistic explanation of GH secretagogue synergy: because ghrelin (and its mimetics like ipamorelin) acts through GHS-R1a while GHRH analogs (CJC-1295, sermorelin, tesamorelin) act through GHRH-R, combining both pathways produces synergistic rather than additive GH release. This is the scientific basis for the CJC-1295/Ipamorelin blend and the Tesamorelin/Ipamorelin blend sold by Ageless Peps.
Related
#research #narrative-review #evidence-level-V #gh-axis #ghrelin