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      Repetitive Injections of L-Glutamic Acid, in Contrast to Those of N-Methyl-D,L-Aspartic Acid, Fail to Elicit Sustained Hypothalamic GnRH Release in the Prepubertal Male Rhesus Monkey (Macaca mulatta)

      research-article
      , ,
      Neuroendocrinology
      S. Karger AG
      Glutamate receptors, Kainate, NMDA, GnRH, Rhesus monkeys

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          Abstract

          The purpose of the present study was to examine whether repetitive intravenous injections of L-glutamic acid (Glu), like those of N-methyl- D, L-aspartic acid (NMA), are able to elicit a sustained train of gonadotropin releasing hormone (GnRH) discharges from the hypothalamus of the prepubertal male monkey. In order to utilize pituitary luteinizing hormone (LH) secretion as a bioassay of hypothalamic GnRH release, the responsiveness of the gonadotroph of the prepubertal animals was enhanced prior to the study with a chronic intermittent intravenous infusion of the synthetic decapeptide (0.1 µg/min for 3 min every h). Sequential intravenous injections of Glu (150 mg/kg BW) were administered at 3-hour intervals for 6 or 24 h. Although the first injection of this acidic amino acid elicited a robust discharge of GnRH, subsequent stimulation with Glu resulted in GnRH discharges with progressively decreasing magnitudes, and by the 9th injection Glu-induced GnRH release was abolished. Peak concentrations of circulating Glu following the 1st and 4th Glu injection were indistinguishable (3,959 ± 437 vs. 4,139 ± 72 nmol/ml, respectively). Interestingly, the failure of repetitive intravenous injections of Glu to sustain pulsatile GnRH release was not associated with a loss of responsiveness to NMA administration, nor was it accompanied by a corresponding decrement in Glu induced growth hormone (GH) discharges. As previously demonstrated, repetitive intravenous administration of NMA (2-5 mg/kg BW) every 3 h for 9 h sustained pulsatile GnRH secretion without decrement. A similar intermittent infusion of kainic acid (KA; 1 mg/kg BW every 3 h for 6 h), however, elicited a GnRH response that mimicked that observed in response to intermittent Glu treatment. These findings are consistent with the notion that Glu administered by intravenous injection fails to reach the central N-methyl-D-aspartic acid (NMDA) receptors that mediate the sustained train of GnRH discharges elicited in response to repetitive intravenous injections of NMA. Instead, circulating Glu appears to activate non-NMDA receptors in the vicinity of the median eminence. Repetitive activation of these non-NMDA receptors, in contrast to that of the NMDA receptor, fails to sustain an intermittent discharge of GnRH. The Glu induced GH release, which occurred without decrement, was therefore presumably mediated by NMDA receptors on GH releasing hormone cells in close proximity to the median eminence.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1992
          1992
          07 April 2008
          : 55
          : 6
          : 660-666
          Affiliations
          Department of Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pa., USA
          Article
          126186 Neuroendocrinology 1992;55:660–666
          10.1159/000126186
          1352860
          37ce6a40-06f0-43e1-98ab-4c35d61e1c36
          © 1992 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
          : 06 May 1991
          : 11 July 1991
          Page count
          Pages: 7
          Categories
          Original Paper

          Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
          Kainate,Rhesus monkeys,Glutamate receptors,GnRH,NMDA

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