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      Growth Hormone Heterogeneity in Human Pituitary and Plasma

      research-article
      Hormone Research in Paediatrics
      S. Karger AG
      Growth hormone, Heterogeneity, Growth hormone-binding protein, Immunoassays

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          Abstract

          Several isoforms of growth hormone (GH) have been identified in humans. There are many reasons for this heterogeneity. At the genetic level, two genes encode GH: GH-N, expressed in the pituitary, and GH-V, expressed in the placenta. At the mRNA level, GH-N undergoes alternative splicing into 20K and 22K isoforms. Post-translationally, 22K GH undergoes modifications, such as acetylation at its amino terminus, deamidation, and oligomerization. The picture is complicated further in the circulation, where GH binds to two GH-binding proteins, each with different affinities for the GH isoforms. In addition, a highly heterogeneous mixture of GH fragments has been demonstrated. The implications of this heterogeneity relate to differences between GH immunoassays, such that assay results cannot be compared between laboratories. The reasons for GH heterogeneity and its practical and clinical implications are considered here.

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          Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women

          I Chapman (1994)
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            Influence of growth hormone binding protein on growth hormone estimation in different immunoassays.

            Growth hormone (GH) quantitation in biological fluids varies depending on the assays employed, and factors which may interfere in the assays include the high affinity GH-binding protein (GHBP). To evaluate this potential effect on GH estimates, we studied the influence of adding increasing amounts of high affinity glycosylated GHBP to normal, acromegalic and GH-deficient sera, which were then processed in four different immunoassays. Two commercial immunometric assays, Delfia and Nichols (assays 1 and 2), and two RIAs, one using a polyethylene glycol (PEG) precipitation (assay 3) and one using wick-chromatography (assay 4) for separation of free and bound 125I-GH, were employed. In the Delfia assays, GH estimates of 11 sera decreased (p < 0.05) to 87.2 +/- 2.6%, 73.0 +/- 2.7% and 60.1 +/- 2.5% (mean +/- SEM) of basal GH estimates with the addition of GHBP in concentrations of 0.54, 2.14 and 6.42 nmol/l, respectively. In the Nichols assay, GH estimates were not significantly reduced (93.4 +/- 2.6%, 83.8 +/- 4.5% and 83.9 +/- 3.9%) with the applied GHBP concentrations. In assay 3 (RIA), the addition of GHBP increased GH estimates to 122 +/- 10.0% and 167 +/- 19.1% (both p < 0.05) with the addition of GHBP in concentrations of 2.14 and 6.42 nmol/l, respectively, whereas an increase in GHBP concentration of 0.54 nmol/l did not change the estimates from basal levels (99.0 +/- 4.8%, p > 0.05). In assay 4 (RIA), the addition of GHBP induced decreased GH estimates. With this varying influence of GHBP on GH estimates, binding protein interference should be taken into consideration when comparing GH estimates obtained with many currently utilized GH immunoassays. The present results demonstrate that GHBP levels within physiological range may interfere with the results of GH assays, giving either spuriously high or low values depending on the GH assay methodology.
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              Author and article information

              Journal
              HRE
              Horm Res Paediatr
              10.1159/issn.1663-2818
              Hormone Research in Paediatrics
              S. Karger AG
              978-3-8055-6898-2
              978-3-318-00450-2
              1663-2818
              1663-2826
              1999
              June 1999
              17 November 2004
              : 51
              : Suppl 1
              : 2-6
              Affiliations
              Center for Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Medical School, Chicago, Ill., USA
              Article
              53128 Horm Res 1999;51(suppl 1):2–6
              10.1159/000053128
              10393484
              5b512850-c503-41fb-9f3a-3013973aeef3
              © 2004 S. Karger AG, Basel

              Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

              History
              Page count
              Tables: 1, References: 22, Pages: 5
              Categories
              Standardization of Growth Hormone Measurement

              Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
              Growth hormone-binding protein,Heterogeneity,Growth hormone,Immunoassays

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