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      Effects of Continuous Infusion of Interleukin 1β on Corticotropin-Releasing Hormone (CRH), CRH Receptors, Proopiomelanocortin Gene Expression and Secretion of Corticotropin, β-Endorphin and Corticosterone

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          Abstract

          A number of recent studies suggest that interleukin 1β (IL-1β) is a major mediator of hypothalamo-pituitary-adrenal (HPA) responses following infectious aggression. We investigated whether IL-1β mediates long-term changes in HP A activity and studied the cellular regulation of the anterior pituitary. To mimic chronically elevated IL-1β production thought to occur during infectious diseases, osmotic pumps (Alzet type) were implanted in the peritoneal cavity of male rats and hIL-1β was infused continuously at rates of 1 or 3 µg/day. Effects of hIL-1β action on plasma ACTH, β-endorphin (β-EP) and corticosterone (CORT) secretion and on anterior pituitary (AP), ACTH and β-EP content were followed. In addition, hypothalamic (HT) CRH mRNA and in AP, CRH receptor (CRH-Rc) mRNA, POMC nuclear primary transcript RNA, POMC nuclear intermediate processing RNA and POMC nuclear and cytoplasmic mRNA were quantified using a highly sensitive solution hybridization nuclease protection assay. Continuous infusion of hIL-1 β stimulated the HPA axis at varying degrees. Increased HT CRH gene expression, AP POMC gene transcription, ACTH and β-EP release occurred only during the first 3 days of the treatment. A long-lasting enhancement of ACTH and β-EP synthesis and of POMC gene expression resulted from activated POMC gene transcription followed by an increased POMC mRNA stability and decreased POMC mRNA turnover. In the AP, stimulation of ACTH and β-EP secretion and POMC gene transcription disappeared after continuous IL-1β treatment, possibly in part due to a refractory process mediated by decreased CRH-Rc gene expression in corticotropes.

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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
          : 65
          : 1
          : 53-63
          Affiliations
          aLaboratoire de Neuroendocrinologie, URA 1310 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, Paris; bLaboratoire de Pharmacologie, URA 1288 CNRS, Faculté de Médecine de Nancy, Vandæuvre, France
          Article
          127164 Neuroendocrinology 1997;65:53–63
          10.1159/000127164
          9032774
          © 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.

          Page count
          Pages: 11
          Categories
          Neuroimmune Interactions

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