Are growth hormone secretagogues (GHS) useful in regulating multiple growth factors, including Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factors (PDGFs), and Transforming Growth Factor-alpha (TGF-a)?

Growth Hormone Secretagogues in Regulating Multiple Growth Factors

Growth hormone secretagogues (GHS) have demonstrated efficacy in regulating multiple growth factors including VEGF, PDGFs, and TGF-α, but their clinical application should be limited to parenteral administration for specific therapeutic indications rather than general growth factor regulation. 1

Mechanism of Action

Growth hormone secretagogues function by:

• Stimulating the GHS receptor in the pituitary and hypothalamus, mimicking an endogenous factor 2
• Working alongside GHRH (growth hormone-releasing hormone) and somatostatin to regulate GH secretion 2
• Promoting pulsatile release of growth hormone, which then influences downstream growth factors 3

Impact on Growth Factors

When administered parenterally, GHS influence multiple growth factors through both direct and indirect pathways:

• VEGF (Vascular Endothelial Growth Factor):

  • Regulated through GH-stimulated pathways 4
  • Important in angiogenesis and vascular permeability 4

• PDGFs (Platelet-Derived Growth Factors):

  • Involved in cell proliferation, migration, and chemotaxis 4
  • Promote neutrophil and macrophage attraction 4
  • Stimulate mesenchymal stem/progenitor cell proliferation 4

• TGF-α (Transforming Growth Factor-alpha):

  • Regulated through GH-dependent pathways 4
  • Involved in cellular proliferation and differentiation processes 4

Clinical Applications

The most evidence-supported applications of GHS for growth factor regulation include:

1. Growth disorders in children and adolescents:

   • Recombinant human GH has shown improvements in pulmonary function, height, weight, and bone mineral content 4
   • GHS may provide a more physiological pattern of GH release compared to exogenous GH 5

2. Bone regeneration and tissue healing:

   • BMPs and PDGF-BB have demonstrated enhancement of bone formation 4
   • PDGF-BB has shown efficacy in periodontal regeneration and root coverage procedures 4

3. Age-related GH decline:

   • GHS can restore GH secretion in older adults to levels seen in younger adults 3
   • This leads to increased fat-free mass and redistribution of fat 3

Administration and Dosing

For effective growth factor regulation:

• Subcutaneous administration of GHS at 30 μg/kg bodyweight daily is the recommended route 1
• Intravenous administration at 1 μg/kg is primarily used for diagnostic testing 1
• Oral administration has poor bioavailability and is not recommended 1

Monitoring Parameters

When using GHS for growth factor regulation, monitor:

• IGF-1 levels to evaluate treatment response 1
• Growth and development parameters (height velocity, skeletal maturation) 1
• Metabolic parameters (glucose, insulin levels) 1

Limitations and Considerations

Important clinical considerations include:

• GHS produce less growth velocity increase than direct somatropin administration 1
• Potential adverse effects include transient facial flushing, injection site pain, and development of GHRH antibodies with prolonged use 1
• Long-term trials are still needed to fully evaluate clinical efficacy and safety 6

Comparative Efficacy

• Direct GH administration remains more potent than GHS for increasing growth factors 5
• However, GHS provide a more physiological and potentially safer profile of GH secretion 5
• The combined administration of GHRH plus GHRP-6 (a GHS) is currently the most powerful releaser of GH 5

Growth hormone secretagogues represent a promising approach to regulating multiple growth factors, but their clinical application should be guided by specific therapeutic goals rather than general growth factor modulation.