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      Characterization of the Effect of Mycoplasma fermentans on the Hypothalamo-Pituitary-Adrenal Axis

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          Abstract

          The mechanisms involved in the activation of the hypothalamus-pituitary-adrenal axis after administration of Mycoplαsma fermentans were examined. Male rats were injected intracerebroventricularly (i.c.v.) with heat-inactivated M. fermentans (6 µg protein/10 µl/rat) or vehicle and were killed 2 h later. M. fermentans caused a significant depletion of corticotropin releasing hormone (CRH-41) content in the median eminence (ME), and elevation of serum ACTH and corticosterone (CS) levels, compared to control levels. Pretreatment with dexamethasone (DEX, 40 µg/kg) markedly inhibited M. fermentans-induced depletion of ME CRH-41 and the increase in serum ACTH and CS. Injection of the type II corticosteroid receptor antagonist RU-38486, but not the type 1 antagonist RU-28318, enhanced the adrenocortical response and completely abolished the inhibitory effect of DEX following M. fermentans. Injection of the catecholamine neurotoxin 6-hydroxydopamine into the ventral noradrenergic bundle, which significantly depleted hypothalamic nor-epinephrine content, or i.c.v. injection of the specific α<sub>1</sub>-adrenergic receptor antagonist prazosin failed to affect the adrenocortical response to M. fermentans. In contrast, these agents markedly inhibited the adrenocortical response following i.c.v. injection of interleukin-1. I.c.v. administration of M. fermentans caused a significant elevation of hypothalamic levels of tumor necrosis factor-α (TNFα), determined by both bioassay and immunoassay. In rats treated with pentoxifylline, an inhibitor of TNFα synthesis, the adrenocortical response to M. fermentans was markedly inhibited. These findings suggest that: (1) M. fermentans-inducedactivation of the pituitary-adrenal axis, and the inhibitory effect of DEX on this response, are mediated by a reduction of CRH-41 release from the ME. (2) The feedback exerted by glucocorticoids is mediated by type II corticosteroid receptors. (3) In contrast to the adrenocortical response to interleukin-1β, the central noradrenergic system does not have an important role in mediating the adrenocortical response to M. fermentans. (4) Hypothalamic TNFα production is probably involved in mediating the adrenocortical activation following M. fermentans.

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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
          : 3
          : 221-228
          Affiliations
          aDepartment of Neurology, Hadassah University Hospital, bThe Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, and cDepartment of Psychology, The Hebrew University of Jerusalem, Israel
          Article
          127241 Neuroendocrinology 1997;66:221–228
          10.1159/000127241
          9380280
          © 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: 8
          Categories
          Adrenocorticotropic Regulation

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