title: Growth hormone and insulin-like growth factor-I counteracts established steroid catabolism in rats by effects on hepatic amino-N degradation.
abstract: OBJECTIVE
  Long-term steroid treatment causes protein wasting. Liver contributes towards this by upregulating ureagenesis. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are anabolic agents with specific hepatic effects. It is unknown whether IGF-I alone and/or in combination with GH have any effect on established hepatic amino-N catabolism during long-term glucocorticoid treatment.
  
  
  METHODS
  We measured the spontaneous (UNSR) and the substrate standardized rate of urea nitrogen synthesis (STUNSR), N-balance and mRNA levels of urea cycle enzymes in controls (placebo) and four longterm steroid treated groups given (1) prednisolone 4 mg/kg/day during 28 days (St) (2) +GH 1 mg/kg/day from day 21-28 (StGH) (3) +IGF-I 1.5 mg/kg/day 21-28 (StIGF) (4) GH +IGF-I (StGHIGF).
  
  
  RESULTS
  Steroid induced weight loss was stepwisely reversed by IGF-I, GH and both. UNSR, STUNSR and mRNA levels of urea cycle enzymes in the liver increased markedly after steroid treatment, and was normalized after co-administration of GH and IGF-I. N-balance improved after GH and IGF-I administration.
  
  
  CONCLUSIONS
  Our results expands the knowledge of beneficial effects of GH on short-term steroid catabolism to include effects of IGF-I and IGF-I combined with GH on long-term steroid catabolism. Both peptides prevent steroid induced hepatic protein wasting and thereby contribute towards whole body anabolism. The effect in vivo is probably due to an effect of the peptides on urea cycle enzyme mRNA.
authors.affiliation: Department of Hepatology V, Aarhus University Hospital, DK-8000 C, Aarhus, Denmark
authors.forename: T
authors.initials: T
authors.lastname: Grøfte
authors.forename: D S
authors.initials: DS
authors.lastname: Jensen
authors.forename: J
authors.initials: J
authors.lastname: Greisen
authors.forename: N
authors.initials: N
authors.lastname: Tygstrup
authors.forename: H
authors.initials: H
authors.lastname: Vilstrup
mesh_terms: D000409:Alanine / Q000494:pharmacology; D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism / Q000652:urine; D011239:Prednisolone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000378:metabolism*; D014018:Tissue Distribution; D014508:Urea / Q000378:metabolism
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D004798:Enzymes; D005938:Glucocorticoids; D007328:Insulin; D012333:RNA, Messenger; D013256:Steroids; D007334:Insulin-Like Growth Factor I; D014508:Urea; D013006:Growth Hormone; D011239:Prednisolone; D009584:Nitrogen; D000409:Alanine