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

Key points Loss of muscle and tendon function during periods of immobilisation and rehabilitation represents a challenge in clinical medicine., It is not known to what extent growth hormone (GH) supplementation is able to counteract the absence of mechanical loading during immobilisation in musculo-tendinous connective tissue., This study examines the effect of GH in musculo-tendinous connective tissue in humans during immobilisation and subsequent rehabilitation., The main study findings were the observation that GH supplementation stimulates collagen expression in musculo-tendinous tissue and abolishes the normal decline in tendon stiffness and lysyl oxidase during immobilisation. Furthermore, GH supplementation results in an increased tendon size and stiffness during rehabilitation., GH supplementation has a matrix-stabilising effect during periods of inactivity and rehabilitation in humans., Abstract 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 human GH (rhGH) (33-50 μg kg⁻¹ day⁻¹) or placebo (Plc), and had one leg immobilised for 2 weeks, followed by 6 weeks of strength training. The cross-sectional area (CSA), maximal muscle strength (maximal voluntary contraction, MVC) and biomechanical properties of the quadriceps muscle and patellar tendon were determined. Muscle and tendon biopsies were analysed for mRNA of collagen (COL1A1/3A1), insulin-like growth factors (IGF-1Ea/Ec), lysyl oxidase (LOX), matrix metalloproteases (MMP-2 and MMP-9), decorin and tenascin-C. Fibril morphology was analysed by transmission electron microscopy (TEM) to detect changes in the fibril diameter distribution. In muscle, CSA and MVC declined with immobilisation and recovered with rehabilitation similarly in both groups. Likewise, both groups showed increased IGF-1Ea/Ec and COL1A1/3A1 expression in muscle during re-training after immobilisation compared with baseline, and the increase was more pronounced when subjects received GH. The tendon CSA did not change during immobilisation, but increased in both groups during 6 weeks of rehabilitation (∼14%). A decline in tendon stiffness after immobilisation was observed only in the Plc group, and an increase during 6 weeks of rehabilitation was observed only in the GH group. IGF-1Ea and COL1A1/3A1 mRNA increased with immobilisation in the GH group only, and LOX mRNA was higher in the GH group than in the Plc group after immobilisation. Both groups showed an increase in MMP-2 with immobilisation, whereas no changes in MMP-9, decorin and tenascin-C were observed. The tendon fibril diameter distribution remained unchanged in both groups. In conclusion, GH stimulates collagen expression in both skeletal muscle and tendon, abolishes the normal inactivity-related decline in tendon stiffness and LOX, and results in increased tendon CSA and stiffness during rehabilitation. GH has a matrix-stabilising effect during periods of inactivity and rehabilitation in humans. [ABSTRACT FROM AUTHOR]