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      Enhanced Endocrine Response to Novel Environment Stress and Endotoxin in Lurcher Mutant Mice

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          Abstract

          Lurcher mutant mice which are mainly known for their cerebellar degeneration, also display a hyperinducibility of proinflammatory cytokines, such as interleukin-1 α and β (IL-1) and tumor necrosis factor α (TNF-α), in peripheral macrophages. To assess whether this increased responsiveness to inflammatory stimuli is accompanied by a higher pituitary-adrenal response, we compared the adrenocorticotropic hormone (ACTH) and corticosterone response of Lc and wild-type mice to intraperitoneal (i.p.) administration of a cytokine inducer, lipopolysaccharide (LPS). Lurcher mice display resting levels of ACTH and corticosterone similar to those of wild-type mice. LPS (1.25 µg/g) induces a corticosterone surge 2-fold higher in Lurcher than in wild-type mice. By contrast, the response to IL-lα (10 ng/g, i.p.) is similar in both genotypes, suggesting that a differential reactivity of the hypothalamo-pituitary adrenal axis to IL-1 does not account for the higher reactivity of Lurcher mice to LPS. To test whether the increased responsiveness of the pituitary-adrenal axis of Lurcher mice generalizes accross stressors, mice were exposed to a novel environment. This condition also induced a surge of ACTH and corticosterone 3.5- and 2-fold higher in Lurcher than in wild-type mice. Prior blockade of IL-1 receptors by injection of IL-1 receptor antagonist (10 µg/g, i.p.) failed to block the response to LPS injection and exposure to novelty. In contrast, immunoneutralization of hypothalamic corticotropin-releasing hormone (CRH) significantly attenuated the ACTH surge and abrogated the difference between Lurcher and wild-type mice in their responses to a novel environment, suggesting that hypothalamic CRH neurons are involved in this excessive response.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1997
          1997
          09 April 2008
          : 66
          : 5
          : 341-347
          Affiliations
          aLaboratoire de Neurobiologie du Développement, Institut des Neurosciences (CNRS URA 1488), Université P.-et-M.-Curie, Paris, bINSERM (U. 297), Laboratoire de Neuroendocrinologie Expérimentale, Marseille, cInstitut Gustave-Roussy, Villejuif, dINSERM (U. 283), Hôpital Cochin, Paris, France
          Article
          127257 Neuroendocrinology 1997;66:341–347
          10.1159/000127257
          9387853
          2d41e82c-9dd2-4a40-a1e2-a61b58e5a253
          © 1997 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
          : 30 December 1996
          : 10 July 1997
          Page count
          Pages: 7
          Categories
          Pituitary Adrenal Axis

          Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
          Interleukins,Lipopolysaccharides,Cerebellum,Stress,Tumor necrosis factor,Adrenal steroids,Corticotropin,Corticotropin-releasing hormone

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