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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 (P0.01 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 (P0.01 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.

Bone loss during immobilization is well documented. Currently, the only means of studying this in human beings is bed rest, which is resource intensive and inconvenient for the subjects. Unilateral lower limb suspension (ULLS) has been suggested as an alternative, but has not previously been demonstrated to cause bone loss. The main aim of our study was to test the hypothesis that ULLS would cause bone loss determined by peripheral quantitative computed tomography (pQCT). We investigated eight young healthy volunteers (19.1 +/- 0.7 years; body mass index, 22.4 +/- 2.6 kg m(-2)), who underwent ULLS for 24 days; their right foot was suspended with a strap attached to the shoulder so the knee angle was 10 deg and they wore a left shoe with a 7.5 cm sole to allow clearance of the right foot and used bilateral crutches to perambulate. Bone scans were obtained by pQCT from the distal epiphyses and from the diaphyses of the tibia in each leg twice before suspension, at days 7, 14 and 21 of the ULLS, and at days 4, 9, 35 and 90 of recovery. After 21 days of ULLS, bone mineral content of the peripheral portion of the epiphysis of the suspended tibia was reduced by 0.89 +/- 0.48% (from 280.9 +/- 34.5 to 278.4 +/- 34.2 mg mm(-1), P0.001) but no changes were observed in its central portion or in the unsuspended tibia. In the peripheral epiphyseal portion, significant bone loss (by 0.32 +/- 0.54%, P = 0.045) occurred as early as day 7 of ULLS. We have demonstrated, for the first time, that in humans bone is lost during ULLS at rates comparable to those seen with bed rest, without alteration in limb fluid volumes thus validating the technique and raising important questions about the mechanisms involved.