Effect of Peptide Therapy on IGF-1 Levels
Peptide therapy can either increase or suppress IGF-1 levels depending on the specific peptide used: growth hormone and growth hormone-releasing peptides potently stimulate systemic IGF-1 production, while recombinant human IGF-1 peptides directly provide IGF-1 activity, and certain peptides like oral estrogen suppress hepatic IGF-1 production.
Growth Hormone-Based Peptide Therapy Increases IGF-1
- Growth hormone is a potent stimulator of systemic IGF-1 levels and has been shown to increase lean body mass in underweight patients with COPD participating in pulmonary rehabilitation programs 1
- Growth hormone and IGF-1 appear to be physiological modulators of myocardial structure and function, with GH activating cardiac cell growth and inducing physiological ventricular remodeling 1
- Growth hormone administration to patients with GH deficiency is associated with increased wall thickness and normalization of cardiac performance through IGF-1 mediated mechanisms 1
- Studies are ongoing to investigate the efficacy and safety of growth hormone-releasing factors to improve body composition and functional capacity, which work by stimulating endogenous IGF-1 production 1
Direct IGF-1 Peptide Replacement Therapy
- Recombinant human IGF-1 (rhIGF-1) administration directly increases IGF-1 levels and bone formation markers in adolescents and adults with anorexia nervosa 1
- In one RCT in adult women with anorexia nervosa, rhIGF-1 combined with oral estrogen led to a 2.8% significant increase in bone mineral density compared to controls 1
- IGF-1 is a bone trophic factor secreted by the liver in response to growth hormone and is also produced locally in an autocrine manner by target tissues such as bone 1
- Localized infusion of IGF-1 peptide results in skeletal muscle hypertrophy through direct stimulation of protein synthesis and satellite cell proliferation 2
Peptides That Suppress IGF-1 Production
- Oral estrogen peptides suppress hepatic IGF-1 production through first-pass liver metabolism, which upregulates synthesis of IGF-1 binding proteins (IGFBP-1) that further reduce IGF-1 bioavailability 1
- The suppressive effects of oral estrogen on hepatic IGF-1 production have been implicated in the lack of efficacy of oral estrogen in improving bone mineral density in energy-deficient states 1
- This suppression is particularly problematic in amenorrhoeic athletes who already have low endogenous IGF-1 concentrations 1
Anabolic Steroid Peptides and IGF-1 Interaction
- Anabolic steroids may improve outcomes through stimulation of protein synthesis either directly or indirectly by interaction with the IGF-1 system 1
- Low-dose anabolic steroids increase fat-free mass through mechanisms that include modulation of the IGF-1 system and regulation of the myostatin gene 1
IGF-1 Peptide Mimetics and Modulators
- Phage-displayed peptide libraries have yielded peptides that bind IGF-binding proteins and produce IGF-like activity at sub-micromolar concentrations, effectively increasing free IGF-1 availability 3
- IGF-1-derived peptides (particularly residues 50-70) can suppress diabetes onset in NOD mice, probably through amplification of Th2-type immune responses 4
- E-peptides (C-terminal extension peptides of IGF-1 propeptides) control IGF-1 bioavailability by facilitating binding to extracellular matrix, preventing systemic circulation and localizing IGF-1 activity 5
- The active tri-peptide (1-3)IGF1 (glycine-proline-glutamate) enhances expression of synaptic markers and increases endogenous IGF-1 expression through different cellular mechanisms than full-length IGF-1 6
Clinical Considerations
Important Caveats for Growth Hormone Therapy
- Growth hormone therapy is expensive and has been associated with undesirable side effects including salt and water retention and impairment in glucose metabolism 1
- Chronic excess of GH and IGF-1 secretion in acromegaly results in biventricular cardiac hypertrophy and can progress to dilated cardiomyopathy with impaired systolic and diastolic performance 1