title: GH receptor blocker administration and muscle-tendon collagen synthesis in humans.
abstract: BACKGROUND
  The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans.
  
  
  OBJECTIVE
  We hypothesised, that a GH blockade would decrease IGF-I and collagen synthesis in the connective tissue of skeletal muscle and tendon.
  
  
  METHODS
  The study was randomised and double blinded.
  
  
  METHODS
  20 healthy young males completed the study.
  
  
  METHODS
  The participants were randomised to 2 weeks of GH receptor blocker supplementation (pegvisomant, 5 mg/day, n=9) or placebo (n=11).
  
  
  METHODS
  Serum levels of GH, IGF-I and IGF-binding protein 3 (IGFBP-3) were measured before and after pegvisomant/placebo supplementation. Fractional synthesis rates (FSR) for collagen and myofibrillar protein were determined with stable isotopes in tendon and muscle, and mRNA for collagen (COL1A1 and COL3A1) as well as IGF-I isoforms (Ea and Ec) were measured in skeletal muscle.
  
  
  RESULTS
  Pegvisomant decreased serum IGF-I by 20% (p<0.01) and serum IGFBP-3 by 10% (p<0.05). Pegvisomant supplementation had no effect on collagen synthesis in tendon and skeletal muscle, nor was muscle myofibrillar protein synthesis affected. Similarly, pegvisomant supplementation had no effect on mRNA expression of IGF-I and collagen in skeletal muscle.
  
  
  CONCLUSIONS
  GH receptor blocker administration in healthy humans resulted in a moderate decrease in serum IGF-I. Collagen synthesis in tendon and skeletal muscle, as well as skeletal muscle IGF-I and collagen mRNA expression, was unaffected by GH receptor blocker supplementation.
authors.affiliation: Institute of Sports Medicine, Dept. of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health Sciences, University of Copenhagen, Denmark. rieharboenielsen@gmail.com
authors.forename: Rie Harboe
authors.initials: RH
authors.lastname: Nielsen
authors.forename: Simon
authors.initials: S
authors.lastname: Doessing
authors.forename: Kazushige
authors.initials: K
authors.lastname: Goto
authors.forename: Lars
authors.initials: L
authors.lastname: Holm
authors.forename: Søren
authors.initials: S
authors.lastname: Reitelseder
authors.forename: Jakob
authors.initials: J
authors.lastname: Agergaard
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvberg
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000328:Adult; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism; D004311:Double-Blind Method; D013006:Growth Hormone / Q000097:blood; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013710:Tendons / Q000378:metabolism*
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003094:Collagen; C406545:pegvisomant