Tendon and skeletal muscle matrix gene expression and functional responses to immobilisation and rehabilitation in young males: Effect of growth hormone administration

We examined the effect of growth hormone (GH) on connective tissue of tendon and skeletal muscle during immobilisation and re-training in humans. Young men (20-30 years; n=20) were randomly assigned to daily recombinant GH (rhGH)(33-50μg/kg/d) or placebo (Plc), and had one leg immobilised for two weeks followed by six weeks of strength training. Cross sectional area (CSA), maximal muscle strength (MVC) and biomechanical properties of m.quadriceps and patellar tendon were determined. Muscle and tendon biopsies were analysed for mRNA of collagen (COL-1A1/3A1), insulin-like growth factors (IGF-1Ea/Ec), lysyloxidase (LOX), matrix metalloproteases (MMP-2 and -9), decorin and tenascin-C. Fibril morphology was analysed by transmission electron microscope (TEM) to detect changes in fibril diameter distribution. In muscle the CSA and MVC declined with immobilisation, and recovered with rehabilitation similar in both groups. Likewise, both groups increased in IGF-1Ea/Ec and COL-1A1/3A1 expression in muscle during re-training after immobilisation compared to baseline, and the rise was more pronounced when subjects recieved GH. The tendon CSA did not change during immobilisation, but increased in both groups during six weeks of rehabilitation (~14%). A decline in tendon stiffness after immobilisation was observed only in Plc, and an increase during six weeks rehabilitation was observed only in GH. IGF-1Ea and COL-1A1/3A1 mRNA increased with immobilisation in the GH group only, and LOX mRNA was after immobilisation higher in the GH group vs Plc. Both groups increased in MMP-2 with immobilisation, whereas no changes in MMP-9, decorin and tenascin-C were observed. Tendon fibril diameter distribution remained unchanged in both groups. In conclusion, GH stimulates collagen expression in both skeletal muscle and tendon and abolishes the normal inactivity related decline in tendon stiffness and LOX, and results in an increased tendon CSA and stiffness during rehabilitation. GH has a matrix stabilising effect during periods with inactivity and rehabilitation in humans.