Description
Ipamorelin – Advanced Biochemical Mechanism Profile
(Selective GHSR-1a Agonist; Growth Hormone Secretagogue Peptide)
Ipamorelin is a synthetic pentapeptide that selectively activates the Growth Hormone Secretagogue Receptor type-1a (GHSR-1a) without significant interaction with ACTH, cortisol, or prolactin pathways observed in some other GHS compounds. GHSR-1a is a G-protein–coupled receptor expressed in hypothalamic neurons and pituitary somatotrophs.
✅ 1. Primary Receptor Target
GHSR-1a (Growth Hormone Secretagogue Receptor-1a)
-
Class: Gq/11-coupled GPCR
-
Main signaling outcome: intracellular Ca²⁺ mobilization → GH vesicle exocytosis
Signaling sequence:
-
Ipamorelin binds extracellular GHSR-1a
-
Gq/11 activation
-
Phospholipase C-β (PLCβ) activated
-
PIP₂ → IP₃ + DAG
-
IP₃ → Ca²⁺ release from ER stores
-
DAG → PKC activation
-
Vesicular GH release in somatotroph models
✅ 2. Intracellular Signaling Cascades
A. PLCβ → IP₃ / DAG → Ca²⁺ and PKC
-
IP₃ opens ER Ca²⁺ channels
-
DAG activates PKC, promoting membrane depolarization
-
Ca²⁺ influx drives GH-containing vesicle fusion
Key enzymes:
-
PLCβ, PKCα/β, IP₃ receptor channels, voltage-gated Ca²⁺ channels
B. cAMP / PKA (Secondary Support Pathway)
Although not the dominant mechanism, some GHSR-1a systems show:
-
↑ adenylate cyclase
-
↑ cAMP
-
PKA phosphorylation of Ca²⁺ channels
-
Enhanced exocytosis priming factors (SNARE proteins)
C. MAPK / ERK1/2 Pathway
-
GHSR-1a → Ras → Raf → MEK → ERK1/2
-
ERK nuclear translocation → gene transcription
-
Research models show upregulation of growth-associated transcription factors (FOS, JUN)
D. PI3K / Akt Crosstalk
Observed in neuronal and pituitary models:
-
PI3K → Akt phosphorylation
-
Cell-survival and mitochondrial-stability signals (BCL2, MCL1)
✅ 3. Second Messengers & Receptor Kinetics
| Component | Activity with Ipamorelin |
|---|---|
| IP₃ | ↑ ER Ca²⁺ release |
| DAG | ↑ PKC activation |
| Ca²⁺ | ↑ Vesicular fusion in GH cells |
| cAMP | Moderate ↑ in some models |
| ERK1/2 | Induced phosphorylation |
| Akt | Crosstalk activation in select tissues |
Ipamorelin has high selectivity for GH release with minimal activity at other endocrine axes compared to older GHS analogs.
✅ 4. Gene Targets Commonly Measured in Research
| Functional Class | Representative Genes |
|---|---|
| GH Axis | GHRH, GHRHR, GH1, IGF-1 |
| Calcium Signaling | CACNA1A, RYR, IP₃ receptor (ITPR genes) |
| MAPK-responsive | FOS, JUN, EGR1 |
| Anti-apoptotic | BCL2, MCL1, SOD2 |
| Exocytosis Machinery | SNAP25, SYT1, STXBP1 |
✅ Summary of Core Mechanisms
-
GHSR-1a activation (Gq/11)
-
PLCβ → IP₃/DAG
-
Ca²⁺ mobilization
-
PKC-dependent vesicle fusion
-
Secondary ERK1/2 and PI3K-Akt signaling
-
Upregulation of growth- and survival-associated genes
Research-Only Classification
Ipamorelin is provided solely for controlled in-vitro laboratory research.
It is not approved for human or animal administration, consumption, injection, or diagnostic/therapeutic use.
