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      Peptides lipocorticotropes dans la maladie de Cushing: études in vitro

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          Abstract

          The immunologic patterns of 3 human pituitary adenomas of Cushing’s disease have been studied after gel exclusion chromatography (Sephadex G-50). The immunologic characteristics were examined with three radioimmunoassays specific for human cor-ticotropin (ACTH). lipotropin (LPH) and β-endorphin (β-End). In cell tumor extracts, chromatographic peaks corresponding to β-LPH, γ-LPH, β-End and ACTH were identified. The ACTH/β-LPH-β-End ratio was 1 in the 3 cases. Additionally, in the 3 cases, a chromatographic peak, partially cross-reacting in the β-End assay, was eluted after β-End, thus suggesting the presence of a fragment of the molecule. In 1 case, a peak of large molecular weight material with N- and C-terminal β-LPH and ACTH immunoreactivity was observed, which corresponded to the precursor material.The release and the effects of various stimuli were studied on dispersed tumor cells in primary culture. The tumor cells had a biphasic basal secretion rate with a rapid increase of ACTH/β-LPH-β-End in the culture medium during the first 2 h. Then the release, studied during 2 days, was slower. Chromatographic studies showed that the β-LPH/β-End ratio was 0.8 in the cells and 0.3 in the medium, due essentially to the release of β-End and β-End-like materials. The cells released ACTH and β-LPH-β-End in equimolar ratio after stimulation with arginine vasopressin (AVP). The maximum effect was obtained with 10-6 M AVP (D50 = 1 10-9 M). Dibutyryl cyclic AMP (2 · 10-3 M) induced maximal release of ACTH/β-LPH-β-End. This stimulation was suppressed by a 48-hour preincubation with dexamethasone (10-8–10-6M). There was no effect of TRH and LH-RH on cell release. Dopamine (10-6M) specifically blocked the release of ACTH/β-LPH-β-End in 1 case. These data showed (a) heterogeneity of chromatographic profiles from case to case; (b) the presence of material in the tumor, cell extracts and culture medium corresponding to fragment(s) of β-End; (c) culture studies demonstrated that tumor cells remain responsive to AVP stimulation and dexamethasone suppression, and (d) the dopamine inhibition of ACTH and β-End release needs further investigation.

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          Author and article information

          Journal
          HRE
          10.1159/issn.0018-5051
          Hormone Research in Paediatrics
          S. Karger AG
          978-3-8055-3410-9
          978-3-318-02126-4
          0018-5051
          2571-6603
          1980
          1980
          25 November 2008
          : 13
          : 4-5
          : 242-258
          Affiliations
          aLaboratoire des Hormones protéiques, Clinique endocrinologique (Prof. J. Vague), bLaboratoire de Médecine expérimentale et cClinique Neurochirurgicale(Prof. J. Paillas), Faculté de Médecine de Marseille, Marseille, France
          Article
          179293 Horm Res 1980;13:242–258
          10.1159/000179293
          © 1980 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.

          Page count
          Pages: 17
          Categories
          Lipo-Corticotropic Hormones and Cushing’s Disease

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