title: Urine metabonomic profiling of a female adolescent with PIT-1 mutation before and during growth hormone therapy: insights into the metabolic effects of growth hormone.
abstract: OBJECTIVE
  Growth hormone (GH) is a protein hormone with important roles in growth and metabolism. The objective of this study was to investigate the metabolism of a human subject with severe GH deficiency (GHD) due to a PIT-1 gene mutation and the metabolic effects of GH therapy using Nuclear Magnetic Resonance (NMR)-based metabonomics. NMR-based metabonomics is a platform that allows the metabolic profile of biological fluids such as urine to be recorded, and any alterations in the profile modulated by GH can potentially be detected.
  
  
  METHODS
  Urine samples were collected from a female subject with severe GHD before, during and after GH therapy, and from healthy age- and sex-matched controls and analysed with NMR-based metabonomics.
  
  
  METHODS
  The samples were collected at a hospital and the study was performed at a research facility.
  
  
  METHODS
  We studied a 17 year old female adolescent with severe GHD secondary to PIT-1 gene mutation who had reached final adult height and who had ceased GH therapy for over 3 years. The subject was subsequently followed for 5 years with and without GH therapy. Twelve healthy age-matched female subjects acted as control subjects.
  
  
  METHODS
  The GH-deficient subject re-commenced GH therapy at a dose of 1 mg/day to normalise serum IGF-1 levels.
  
  
  METHODS
  Urine metabolic profiles were recorded using NMR spectroscopy and analysed with multivariate statistics to distinguish the profiles at different time points and identify significant metabolites affected by GH therapy.
  
  
  RESULTS
  NMR-based metabonomics revealed that the metabolic profile of the GH-deficient subject altered with GH therapy and that her profile was different from healthy controls before, and during withdrawal of GH therapy.
  
  
  CONCLUSIONS
  This study illustrates the potential use of NMR-based metabonomics for monitoring the effects of GH therapy on metabolism by profiling the urine of GH-deficient subjects. Further controlled studies in larger numbers of GH-deficient subjects are required to determine the clinical benefits of NMR-based metabonomics in subjects receiving GH therapy.
authors: The University of Queensland, Obesity Research Centre, Institute for Molecular Bioscience, St. Lucia, Queensland 4072, Australia.
authors: Shaffinaz
authors: S
authors: Abd Rahman
authors: Horst Joachim
authors: HJ
authors: Schirra
authors: Agnieszka M
authors: AM
authors: Lichanska
authors: Tony
authors: T
authors: Huynh
authors: Gary M
authors: GM
authors: Leong
mesh_terms: D000293:Adolescent; D054316:Biomarkers, Pharmacological / Q000378:metabolism / Q000652:urine; D016022:Case-Control Studies; D004393:Dwarfism, Pituitary / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D057238:Growth Charts; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D020125:Mutation, Missense / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D050817:Transcription Factor Pit-1 / Q000235:genetics*; D016482:Urinalysis / Q000379:methods
chemical_list: D054316:Biomarkers, Pharmacological; D050817:Transcription Factor Pit-1; D019382:Human Growth Hormone