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    Effect of severe growth hormone (GH) deficiency due to a mutation in the GH-releasing hormone receptor on insulin-like growth factors (IGFs), IGF-binding proteins, and ternary complex formation throughout life.

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    Authors
    Aguiar-Oliveira, Manuel H
    Gill, Matthew S
    De A Barretto, Elenilde S
    Alcântara, Marta R
    Miraki-Moud, Farideh
    Menezes, Carlos A
    Souza, Anita H O
    Martinelli, C E
    Pereira, F A
    Salvatori, Roberto
    Levine, Michael A
    Shalet, Stephen M
    Camacho-Hubner, Cecilia
    Clayton, Peter E
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    Affiliation
    Department of Endocrinology, Federal University of Sergipe, Aracaju, Brazil.
    Issue Date
    1999-11
    
    Metadata
    Show full item record
    Abstract
    Measurement of the insulin-like growth factors (IGFs) and their binding proteins has become commonplace in the indirect assessment of the integrity of the GH axis. However, the relative effect of GH deficiency (GHD) on each component of the IGF axis and the merit of any one parameter as a diagnostic test have not been defined in a homogeneous population across all ages. We therefore measured IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, IGFBP-3, and acid labile subunit (ALS) in 27 GHD subjects (aged 5-82 yr) from an extended kindred in Northeast Brazil with an identical GHRH receptor mutation and in 55 indigenous controls (aged 5-80 yr). The effect of GHD on the theoretical distribution of IGFs between the IGFBPs and the ternary complex was also examined. All components of the IGF axis, measured and theoretical, showed complete separation between GHD and control subjects, except IGFBP-1 and IGFBP-2 concentrations, which did not differ. The most profound effects of GHD were on total IGF-I, IGF-I in the ternary complex, and ALS. The proportion of IGF-I associated with IGFBP-3 remained constant throughout life, but was significantly lower in GHD due to an increase in IGF-I/IGFBP-2 complexes. IGF-I in the ternary complex was determined principally by concentrations of ALS in GHD and IGFBP-3 in controls, implying that ALS has greater GH dependency. In the controls, IGF-II was associated primarily with IGFBP-3 and to a lesser extent with IGFBP-2, whereas in GHD the reverse was found. There was also a dramatic decline in the proportion of free ALS in GHD adults that was not evident in controls. As diagnostic tests, IGF-I in the ternary complex and total IGF-I provided the greatest separation between GHD and controls in childhood. Similarly, in older adults the best separation was achieved with IGF-I in the ternary complex, with free ALS being optimal in younger adults. Severe GHD not only reduces the amounts of IGFs, IGFBP-3, and ALS, but also modifies the distribution of the IGFs bound to each IGFBP. Diagnostic tests used in the investigation of GHD should be tailored to the age of the individual. In particular, measurement of IGF-I in the ternary complex may prove useful in the diagnosis of GHD in children and older adults, whereas free ALS may be more relevant to younger adults.
    Citation
    Effect of severe growth hormone (GH) deficiency due to a mutation in the GH-releasing hormone receptor on insulin-like growth factors (IGFs), IGF-binding proteins, and ternary complex formation throughout life. 1999, 84 (11):4118-26 J. Clin. Endocrinol. Metab.
    Journal
    The Journal of Clinical Endocrinology and Metabolism
    URI
    http://hdl.handle.net/10541/87910
    DOI
    10.1210/jc.84.11.4118
    PubMed ID
    10566659
    Type
    Article
    Language
    en
    ISSN
    0021-972X
    ae974a485f413a2113503eed53cd6c53
    10.1210/jc.84.11.4118
    Scopus Count
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