Tesamorelin: Mechanism of Action

1. Receptor Target — GHRH Receptor

Tesamorelin acts como um(a) specific agonist para o(a) GHRH receptor (GHRHr), a seven-transmembrane G protein-coupled receptor (GPCR) located on somatotroph cells no(a) anterior pituitary gland. Binding potency is comparable to endogenous GHRH. [7]

2. DPP-4 Resistance

The trans-3-hexenoic acid modification no(a) N-terminal Tyr1 acts como um(a) chemical shield against DPP-4 cleavage. Native GHRH is rapidamente degradado(a) (T½ ~5 min); Tesamorelin's modification extends stability to ~26–38 min. [3]

3. Sinalizacao a Jusante Cascade

Gₛ → Adenylyl Cyclase → cAMP → PKA → Ca²⁺ Influx → GH Exocytosis:

1. Receptor ativacao desencadeia the Gₛα subunit
2. Gₛα estimula adenylyl cyclase, converting ATP to cAMP
3. Elevated cAMP ativa Protein Kinase A (PKA)
4. PKA opens voltage-gated Ca²⁺ channels → calcium influx
5. Ca²⁺ desencadeia exocytosis of pre-stored GH vesicles
6. Simultaneamente, cAMP promove GH gene transcricao (new GH synthesis) [7]

The product supplied here is for uso em pesquisa apenas independentemente de regulatory status of related formulations.

4. Selectivity

Tesamorelin is highly selective para o(a) GHRH receptor. It does not significantly alter TSH, LH, ACTH, or Prolactin levels. Diferentemente de GHRPs (e.g., Ipamorelin), it nao bind the ghrelin receptor. [9]

5. Cellular and Tissue-Level Effects

Adipose Tissue:

• Selectively reduz visceral tecido adiposo (VAT) by ~15–18%, minimal effect on subcutaneo(a) fat [10]
• Activates hormone-sensitive lipase (HSL), inibe lipoprotein lipase (LPL)
• Visceral fat cells have higher GH receptor density, explaining selectivity

Hepatic (Liver):

• Reduces hepatico(a) fat (~37% relative reduction) [11]
• Reduces de novo lipogenesis, aprimora fatty acid oxidation
• Prevents progression of liver fibrose (10.5% vs 37.5% progression, P=0.04) [11]

Musculoskeletal:

• Promotes protein synthesis, aumenta trunk lean mass and muscle area [12]
• Improves muscle density (myosteatosis reduction)

Nervous System:

• Improves executive function and verbal memory in MCI/aging [13]
• Increases GABA levels, modula amyloid-beta pathways

6. Comparison with Related Molecules

7. Pharmacokinetics

Parameter	Value
Route	Subcutaneous (abdomen)
Bioavailability	<4% (SC)
Half-Life (T½)	~26–38 min (SC, 2 mg); ~11 min (1.28 mg WR)
Standard Dose	2 mg SC daily (SV); 1.28 mg SC daily (WR)
GH Pulsatility	Preserved (natural pulses, IGF-1 feedback intact)
Metabolism	Proteolytic cleavage; no formal human metabolismo studies
Animal T½	21–45 min (dogs)