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      Chronic Central Infusion of Growth Hormone Secretagogues: Effects on Fos Expression and Peptide Gene Expression in the Rat Arcuate Nucleus

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          Abstract

          Growth hormone (GH) secretagogues induce GH release, in part, by direct actions upon anterior pituitary somatotropes and, in part, by actions upon the neuroendocrine circuitry that regulates GH secretion. In particular, acute systemic administration of GH secretagogues results in increased neuronal activity and Fos protein expression in the arcuate nucleus of the hypothalamus. Prolonged administration of GH secretagogues has been reported to have long-lasting effects upon GH release, promoting increased pulsatile secretion. Here, we investigated how chronic central infusion of GH secretagogues affects the response of arcuate nucleus neurons to acute systemic administration of GH secretagogues. In male rats, after central infusion of GH secretagogues for 5 days, there was no sustained expression of Fos in the arcuate nucleus, no significant induction of Fos expression in response to acute GH secretagogue challenge, and a greatly attenuated secretion of GH in response to acute GH secretagogue challenge, all reflecting loss of funtional responsiveness to GH secretagogues. In situ hybridisation revealed that, in the arcuate nucleus of GH secretagogue-infused rats, mRNA levels for GH-releasing hormone, neuropeptide Y and somatostatin were not different than in saline-infused animals. However, somatostatin mRNA levels in the periventricular nuclei of GH secretagogue-infused rats were significantly higher than those of saline-infused rats, indicating that this nucleus may play an important role in mediating the effects of chronic GH secretagogue administration.

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          Most cited references 7

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          Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues

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            Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons.

            The synthetic hexapeptide growth hormone-releasing peptide selectively releases growth hormone in many species including man. Growth hormone-releasing peptide directly stimulates growth hormone release by an action at the level of the pituitary, at a different receptor site to that for the endogenous 44-amino acid peptide, growth hormone-releasing hormone, and when administered with growth hormone-releasing hormone has a synergistic effect. In addition to this pituitary action, we have suggested that the potent in vivo growth hormone-releasing activity of growth hormone-releasing peptide reflects a hypothalamic action and growth hormone-releasing peptide binding sites have been reported to be present in the hypothalamus. We have now found more direct evidence for a hypothalamic action of growth hormone-releasing peptide in two ways. First, we have found that a sub-population of hypothalamic neurons show strongly increased fos expression in response to systemic growth hormone-releasing peptide administration. Fos is the protein product of the immediate early gene, c-fos, which is induced in many neuronal systems following their activation. Second, extracellular recordings from putative growth hormone-releasing hormone neurons in the arcuate nucleus showed that growth hormone-releasing peptide also stimulates the firing of neurons in this area.
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              Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP- 6 main action is exerted at the hypothalamic level

               V. Popović (1995)
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                1999
                August 1999
                16 August 1999
                : 70
                : 2
                : 83-92
                Affiliations
                aDepartment of Biomedical Sciences, University Medical School, Edinburgh; bDepartment of Physiology, University of Cambridge, UK; cDepartment of Biochemistry and Physiology, Merck Research Laboratories, Rahway, N.J., USA
                Article
                54462 Neuroendocrinology 1999;70:83–92
                10.1159/000054462
                10461022
                © 1999 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
                Figures: 5, References: 40, Pages: 10
                Categories
                Growth Hormone-Releasing Hormone and Growth Hormone Secretagogues

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