Effect of growth hormone on aging connective tissue in muscle and tendon: gene expression, morphology, and function following immobilization and rehabilitation

J Appl Physiol (1985). 2014 Jan 15;116(2):192-203. doi: 10.1152/japplphysiol.01077.2013. Epub 2013 Nov 14.

Abstract

It is unknown whether loss in musculotendinous tissue during inactivity can be counteracted by growth hormone (GH), and whether GH accelerate rehabilitation in aging individuals. Elderly men (65-75 yr; n = 12) had one leg immobilized 2 wk followed by 6 wk of retraining and were randomly assigned to daily injections of recombinant GH (rhGH; n = 6) or placebo (Plc; n = 6). Cross-sectional area (CSA), muscle strength (MVC), and biomechanical properties of m. quadriceps and patellar tendon were determined. Muscle and tendon biopsies were analyzed for gene expressions (mRNA) of collagen (COL1A1/3A1) and insulin-like growth factors (IGF-1Ea/Ec). Fibril morphology was analyzed by transmission electron microscope (TEM). In tendon, CSA and biomechanical properties did not change following immobilization, but an increase in CSA was found after 6 wk of rehabilitation in both groups. The changes were more pronounced when GH was injected. Furthermore, tendon stiffness increased in the GH group. Muscle CSA declined after immobilization in the Plc but not in the GH group. Muscle CSA increased during retraining, with a significantly larger increase in the GH group compared with the Plc group. Both a time and a group effect were seen for IGF-1Ea/Ec and COL1A1/3A1 mRNA expression in muscle, with a difference between GH and Plc. IGF-1Ea/Ec and COL-1A1/3A1 mRNA expression increased in muscle following immobilization and retraining in subjects receiving GH, whereas an increase in IGF-1Ec mRNA expression was seen in the Plc group only after retraining. In conclusion, in elderly humans, GH seems to have a matrix stabilizing effect during inactivity and rehabilitation by stimulating collagen expression in the musculotendinous tissue and increasing tendon CSA and stiffness.

Keywords: connective tissue; growth hormone; inactivity; skeletal muscle; tendon.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Connective Tissue / drug effects*
  • Connective Tissue / metabolism
  • Double-Blind Method
  • Gene Expression / drug effects
  • Human Growth Hormone / administration & dosage*
  • Humans
  • Immobilization / methods
  • Injections, Subcutaneous
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Muscle Strength / drug effects
  • Muscle Strength / genetics
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • RNA, Messenger / genetics
  • Recombinant Proteins / administration & dosage
  • Resistance Training
  • Tendons / drug effects*
  • Tendons / metabolism

Substances

  • COL3A1 protein, human
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Collagen Type III
  • RNA, Messenger
  • Recombinant Proteins
  • Human Growth Hormone
  • Insulin-Like Growth Factor I