title: Short-term growth hormone or IGF-I administration improves the IGF-IGFBP system in arthritic rats.
abstract: OBJECTIVE
  Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that inhibits the GH-IGF-I axis and decreases body weight gain and muscle mass. Although chronic GH or IGF-I treatment increases body weight gain in arthritic rats, muscle resistance to GH and IGF-I is a very common complication in inflammatory diseases. In this study we examine the effect of short-term administration of rhGH and rhIGF-I on liver and muscle IGF-I, IGFBP-3 and -5 as well as on the ubiquitin-ligases MuRF1 and atrogin-1 in the muscle of arthritic rats.
  
  
  METHODS
  Arthritis was induced in adult male Wistar rats by an intradermal injection of 4 mg of Freund's adjuvant. Fifteen days after adjuvant injection, 300 μg/kg of rhGH or 200 μg/kg of rhIGF or saline was administrated 18 and 3h before decapitation. A pair-fed group injected with saline was included in order to discard a possible effect of decreased food intake. Gene expression of IGF-I, GHR, IGFBP-3, IGFBP-5, atrogin-1 and MuRF1 were quantified using RT-PCR. In serum, IGF-I was measured by radioimmunoassay (RIA) and IGFBP-3 by ligand blot.
  
  
  RESULTS
  Arthritis decreased serum IGF-I and IGF mRNA in liver (P<0.05), but not in skeletal muscle. In arthritic rats, rhGH increased serum IGF-I and liver IGF-I mRNA similar to the levels of pair-fed rats. Arthritis increased atrogin-1, MuRF1, IGFBP-3 and IGFBP-5 mRNA in muscle (P<0.01). IGFBP-3 mRNA was downregulated by rhIGF-I, but not by rhGH, administration in control and arthritic rats (P<0.05). Administration of rhGH and rhIGF-I increased IGFBP-5 in the gastrocnemius of arthritic rats.
  
  
  CONCLUSIONS
  Short-term rhGH and rhIGF-I administration was found to increase muscle IGFBP-5 mRNA, whereas only rhIGF-I administration decreased muscle IGFBP-3 mRNA in control and arthritic rats. These data suggest that arthritis does not induce GH or IGF-I resistance in skeletal muscle.
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Avda. Complutense s/n. 28040 Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López-Menduiña
authors.forename: A I
authors.initials: AI
authors.lastname: Martín
authors.forename: E
authors.initials: E
authors.lastname: Castillero
authors.forename: M A
authors.initials: MA
authors.lastname: Villanúa
authors.forename: A
authors.initials: A
authors.lastname: López-Calderón
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone