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Dose dependency of the serum bio/immuno GH ratio in children during pharmacological secretion tests

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Abstract

Dissociation between GH bioactivity (bio-GH) and GH immunoactivity (immuno-GH) is due to the heterogeneity of the molecule: the measurements do not always provide reliable information on the bio-GH. We studied the ratio of bio-GH and immuno-GH during pharmacological secretion tests in 211 sera to study the concentration-response curve of the assay (C1 ), 16 samples of normally growing subjects with idiopathic short stature (C2), 13 samples from patients with GH deficiency (GHD1) and 6 samples of 3 patients with GHD and normal provocative tests (GHD2). GH bioactivity was determined by the Nb2 cell proliferation assay (bio-GH) and immuno-GH by a time-resolved immunofluorometric assay (IFMA) (immuno-GH). A non-linear negative relationship between the serum bio-GH/immuno-GH ratio and serum immuno-GH was observed in C1. In log-log plotting representation, two cut-off lines were drawn: a vertical cut-off line separating above-below cut-off serum peak immuno-GH values in provocative tests, and a diagonal cut-off line separating normal-abnormal serum bio-GH/immuno-GH ratio; four areas were defined. GHD1 had normal ratios, but below cut-off peak immuno-GH responses. P2 and P3 of Group GHD2 had abnormal ratios in samples with low serum immuno-GH but only P2 had autosomal dominant mutation. P1 had the same autosomal dominant isolated GHD as P2 but a low normal ratio. Our data underline the importance of relatively low serum GH concentrations in mediating GH biological actions. An abnormal serum bio-GH/immuno-GH ratio might explain certain cases of GHD and might be useful in detecting abnormal circulating isoforms of GH in patients with growth failure.

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Authors and Affiliations

  1. Endocrinology Laboratory, Garrahan Pediatric Hospital, Buenos Aires, Argentina

    E. A. Chaler, R. Marino, E. Berensztein, M. Maceiras, M. A. Rivarola & A. Belgorosky

  2. Department of Pediatrics, University of Pavia, Italy

    P. Travaglino, S. Pagani, E. Bozzola & M. Bozzola MD

  3. Department Pediatric, Purpan Hospital, Toulouse, France

    M. Tauber

Authors
  1. E. A. Chaler
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  2. P. Travaglino
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  3. S. Pagani
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  4. E. Bozzola
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  5. R. Marino
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  6. E. Berensztein
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  7. M. Maceiras
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  8. M. Tauber
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  9. M. A. Rivarola
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  10. A. Belgorosky
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  11. M. Bozzola MD
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Corresponding author

Correspondence to M. Bozzola MD.

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Chaler, E.A., Travaglino, P., Pagani, S. et al. Dose dependency of the serum bio/immuno GH ratio in children during pharmacological secretion tests. J Endocrinol Invest 29, 109–114 (2006). https://doi.org/10.1007/BF03344082

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  • DOI: https://doi.org/10.1007/BF03344082

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