title: Increased protein turnover and proteolysis is an early and primary feature of short-term experimental hyperthyroidism in healthy women.
abstract: BACKGROUND
  Hyperthyroidism increases energy expenditure, glucose turnover, lipolysis, and protein breakdown.
  
  
  OBJECTIVE
  Our objective was to test whether increased protein breakdown occurs independently of other catabolic effects in mild experimental hyperthyroidism.
  
  
  METHODS
  We conducted a single-blind, randomized, placebo-controlled, crossover study. Protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique ([(15)N]phenylalanine and [(2)H(4)]tyrosine). All subjects underwent a 3-h study in the basal state followed by a 3-h euglycemic clamp study.
  
  
  METHODS
  The study took place at a university clinical research unit.
  
  
  METHODS
  Eight healthy women (24-46 yr old) participated.
  
  
  METHODS
  Intervention included 6 d thyroid hormone (T(4) 50 microg and T(3) 0.67 microg/kg.d) or placebo administration.
  
  
  RESULTS
  Thyroid hormone administration led to mild T(3) hyperthyroidism with more than a doubling of T(3) levels and suppression of TSH. Energy expenditure and body composition was unchanged. Glucose infusion rates, forearm glucose uptake, and levels of lipid intermediates were also alike. Basal whole-body phenylalanine flux and tyrosine flux (reflecting whole-body protein breakdown) were increased (P < 0.05) as were whole-body protein synthesis rate (P = 0.05). Basal forearm rate of appearance and disappearance for phenylalanine (reflecting muscle protein breakdown and synthesis) were similar.
  
  
  CONCLUSIONS
  Mild short-term experimental hyperthyroidism increases whole-body protein turnover and breakdown before any measurable changes in energy expenditure or glucose and fat metabolism, suggesting that amino acid and protein metabolism is an early and primary target for thyroid hormone action in humans.
authors.affiliation: Medical Department M, Aarhus University Hospital, 8000 Aarhus C, Denmark. anne.lene.riis@ki.au.dk
authors.forename: Anne Lene Dalkjaer
authors.initials: AL
authors.lastname: Riis
authors.forename: Jens Otto Lunde
authors.initials: JO
authors.lastname: Jørgensen
authors.forename: Per
authors.initials: P
authors.lastname: Ivarsen
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Jørgen
authors.initials: J
authors.lastname: Weeke
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
mesh_terms: D000328:Adult; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D018592:Cross-Over Studies; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D006262:Health; D006801:Humans; D006980:Hyperthyroidism / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D007333:Insulin Resistance; D008875:Middle Aged; D009132:Muscles / Q000737:chemistry / Q000187:drug effects; D010919:Placebos; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism*; D016037:Single-Blind Method; D013963:Thyroid Hormones / Q000009:adverse effects* / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000596:Amino Acids; D010919:Placebos; D011506:Proteins; D013963:Thyroid Hormones