Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis

Abstract

In skeletal muscle and tendon the extracellular matrix confers important tensile properties and is crucially important for tissue regeneration after injury. Musculoskeletal tissue adaptation is influenced by mechanical loading, which modulates the availability of growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I), which may be of key importance. To test the hypothesis that GH promotes matrix collagen synthesis in musculotendinous tissue, we investigated the effects of 14 day administration of 33-50 microg kg(-1) day(-1) recombinant human GH (rhGH) in healthy young individuals. rhGH administration caused an increase in serum GH, serum IGF-I, and IGF-I mRNA expression in tendon and muscle. Tendon collagen I mRNA expression and tendon collagen protein synthesis increased by 3.9-fold and 1.3-fold, respectively (P < 0.01 and P = 0.02), and muscle collagen I mRNA expression and muscle collagen protein synthesis increased by 2.3-fold and 5.8-fold, respectively (P < 0.01 and P = 0.06). Myofibrillar protein synthesis was unaffected by elevation of GH and IGF-I. Moderate exercise did not enhance the effects of GH manipulation. Thus, increased GH availability stimulates matrix collagen synthesis in skeletal muscle and tendon, but without any effect upon myofibrillar protein synthesis. The results suggest that GH is more important in strengthening the matrix tissue than for muscle cell hypertrophy in adult human musculotendinous tissue.

Figure 1. Circulating concentrations of GH, IGF-I, IGF-BP-1 and IGF-BP-3 in young male participants (n= 10) that were studied over 14 days in a crossover design with rhGH/placebo supplementation

Data are means ±s.e.m.*Difference between rhGH supplementation and placebo P < 0.05. **Difference between rhGH and placebo P < 0.01.

Figure 3. Tendon collagen mRNA expression and protein fractional synthetic rate

Young male participants (n= 10) were studied over 14 days in a crossover design with rhGH/placebo supplementation. Data for exercise effect on tendon mRNA are not shown due to repeated biopsy effect (see text for details). Data are geometric means ± back-transformed s.e.m. A, collagen I mRNA. B, collagen III mRNA. C, protein fractional synthesis rate. *Difference between rhGH and placebo P < 0.05. **Difference between rhGH and placebo P < 0.01.

Figure 2. Local IGF-I isoform mRNA expression in human skeletal muscle and tendon

Young male participants (n= 10) were studied over 14 days in a crossover design with rhGH/placebo supplementation. Data for exercise effect on tendon mRNA is not shown due to repeated biopsy effect (see text for details). Data are geometric means ± back-transformed s.e.m. A, tendon IGF-IEa. B, muscle IGF-IEa. C, muscle IGF-IEc. **Difference between rhGH and placebo P < 0.01.

Figure 4. Muscle collagen mRNA expression and protein fractional synthesis rate, and muscle myofibrillar protein fractional synthesis rate

Young male participants (n= 10) were studied over 14 days in a crossover design with rhGH/placebo supplementation. Data are mean ±s.e.m. A, collagen I mRNA. B, collagen III mRNA. C, myofibrillar protein fractional synthesis rate. D, collagen protein fractional synthesis rate. (*) Difference between rhGH and placebo P= 0.06. **Difference between rhGH and placebo P < 0.01.