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:

1. Ipamorelin binds extracellular GHSR-1a

2. Gq/11 activation

3. Phospholipase C-β (PLCβ) activated

4. PIP₂ → IP₃ + DAG

5. IP₃ → Ca²⁺ release from ER stores

6. DAG → PKC activation

7. 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

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

✅ 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.