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      Somatotropic Dysregulation in Old Mammals

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          Abstract

          In old mammals, including humans, the spontaneous growth hormone (GH) secretory pattern is markedly reduced resulting in lower amounts of GH released over 24 h, and the GH response to administration of GH-releasing hormone (GHRH) is reduced. In agreement with these in vivo findings, an impaired responsiveness to GHRH is evident in the pituitary of old male and female rats in vitro, and this is linked with a diminished stimulation of adenylate cyclase by GHRH. The poor GH responsiveness to GHRH in old mammals, which in the rat is coupled to a defective number of GHRH receptors in the somatotrophs, is likely due to a primary deficiency of GHRH availability, as implied by the diminished GHRH immunoreactivity and gene expression in and GHRH release from the hypothalamus of old rats. Attempts have been made to stimulate the sluggish somatotrophic function in elderly humans and dogs using GHRH; in either species positive results were obtained though, overall, it would seem that the GHRH hypofunction does not entirely account for the GH hyposecretory state during ageing. Concerning somatostatin, although the expression of this peptide decreases with age in the rat hypothalamus, secretion and activity of this hormone is increased, resulting in an altered relationship between GHRH and somatostatin gene expression and secretion. It is likely that defects, especially in catecholaminergic and cholinergic neurons, are instrumental in altering specific peptidergic neurons. Reportedly, catecholamines induce GH release by stimulating GHRH neurons and inhibiting somatostatin-releasing neurons; acetylcholine stimulates GH release via muscarinic receptors, in this way inhibiting the action of somatostatin neurons. In old beagle dogs short-term administration of the α<sub>2</sub>-adrenoceptor clonidine strikingly potentiated GHRH-stimulated GH release, thus implying that clonidine was acting via inhibition of hypothalamic release of somatostatin, and the combination GHRH plus clonidine was highly effective in restoring the pulsatile release of GH and plasma IGF-1 levels. The possibility is envisaged that GHRH or other GH-releasing peptides, e.g. GH-releasing hexapeptide (GHRP-6) and hexarelin, given in conjunction with compounds allegedly capable of reducing somatostatinergic function (clonidine, arginine) may be potent pharmacologic tools to reinstate in old humans GH secretion in a physiologic, pulsatile manner.

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          Author and article information

          Journal
          HRE
          10.1159/issn.0018-5051
          Hormone Research in Paediatrics
          S. Karger AG
          978-3-8055-6124-2
          978-3-318-01661-1
          0018-5051
          2571-6603
          1995
          1995
          05 December 2008
          : 43
          : 1-3
          : 39-45
          Affiliations
          Department of Pharmacology, University of Milan, Italy; Europeptides, Argenteuil, France
          Article
          184235 Horm Res 1995;43:39–45
          10.1159/000184235
          7721260
          © 1995 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: 7
          Categories
          Endocrine Functions and Ageing

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