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
| Autor: | Tony Huynh, Shaffinaz Abd Rahman, Horst Joachim Schirra, Agnieszka M. Lichanska, Gary M. Leong |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Adolescent Hormone Replacement Therapy Endocrinology Diabetes and Metabolism Mutation Missense Female adolescent Urine Gene mutation Biology Urinalysis Growth hormone Biomarkers Pharmacological Endocrinology Internal medicine medicine Humans Metabolomics Growth Charts Dwarfism Pituitary Nuclear Magnetic Resonance Biomolecular Human Growth Hormone Control subjects Metabolic effects Case-Control Studies Metabolome Female Transcription Factor Pit-1 GH Deficiency Hormone Follow-Up Studies |
| Zdroj: | Growth hormoneIGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 23(1-2) |
| ISSN: | 1532-2238 |
| Popis: | 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. Design 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. Setting The samples were collected at a hospital and the study was performed at a research facility. Participants 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. Intervention The GH-deficient subject re-commenced GH therapy at a dose of 1 mg/day to normalise serum IGF-1 levels. Main outcome measures 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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