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      Further Evidence of Cholinergic Impairment of the Neuroendocrine Control of the GH Secretion in Down’s Syndrome

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          Abstract

          There are data indicating that cholinergic activity is precociously impaired in Down’s syndrome (DS). On the other hand, acetylcholine as well as arginine (ARG) play a major stimulatory role in the neural control of growth hormone (GH) secretion in humans, likely acting via the inhibition of hypothalamic somatostatin release. The aim of the present study was to verify the effects of pyridostigmine (PD, 120 mg p.o.), a cholinesterase inhibitor, and ARG (0.5 g/kg i.v.) on the growth hormone-releasing hormone (GHRH) (1 µg/kg i.v.)-induced GH rise in 15 adult patients with DS (M/F: 8/7; age 26.5 ± 2.2 years; body mass index, BMI: 25.7 ± 1.0 kg/m<sup>2</sup>) in which the potentiating effect of PD on GH secretion has been reported to be reduced. The results in DS were compared to those in 15 normal subjects (NS) (M/F: 8/7; age: 30.0 ± 1.3 years; BMI: 21.4 ± 0.4 kg/m<sup>2</sup>). Basal GH and insulin growth factor I (IGF-1) levels in DS (1.8 ± 0.7 and 206.5 ± 21.0 µg/l) were similar to those in NS (1.4 ± 0.3 and 179.4 ± 11.0 µg/l). The GH response to GHRH alone in DS (526.5 ± 120.1 µg/l/h) was lower (p < 0.05) than that recorded in NS (895.4 ± 153.7 µg/l/h). The GHRH-induced GH rise was potentiated by PD both in DS (1,138 ± 184.2 µg/l/h; p < 0.02 vs. GHRH alone) and in NS (2,213.8 ± 212.8 µg/l/h; p < 0.005 vs. GHRH alone); however, as the percent potentiating effect of PD was similar in both groups (215 and 247%, respectively) the GH response to GHRH+PD in DS was lower (p < 0.005) than that in NS. The GHRH-induced GH rise was also potentiated by ARG in both DS (2,243 ± 362.4 µg/h; p < 0.001 vs. GHRH alone) and NS (2,764.3 ± 325.7 µg/l/h; p < 0.005 vs. GHRH alone). As the percent potentiating effect of ARG in DS was more marked than in NS (425 vs. 308%, respectively), the GH response to GHRH+ARG became similar in both groups. No sex-related difference was found in the GH response to various stimuli both in DS and NS. In conclusion, these data demonstrate that the potentiating effect of PD but not that of ARG is impaired in adults with DS in whom a reduced somatotrope responsiveness to GHRH is present. These findings indicate that in DS the pituitary GH releasable pool is fully preserved while an impairment of the tuberoinfundibular cholinergic pathways could lead to somatostatinergic hyperactivity and low somatotrope responsiveness to GHRH.

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          Author and article information

          Journal
          DEM
          Dement Geriatr Cogn Disord
          10.1159/issn.1420-8008
          Dementia and Geriatric Cognitive Disorders
          S. Karger AG
          1420-8008
          1421-9824
          1998
          April 1998
          20 February 1998
          : 9
          : 2
          : 78-81
          Affiliations
          a Paediatric Department, Endocrine Unit, Scientific Institute H San Raffaele, University of Milan, b Division of Endocrinology, Department of Internal Medicine, University of Turin, Italy
          Article
          17027 Dement Geriatr Cogn Disord 1998;9:78–81
          10.1159/000017027
          9524798
          © 1998 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: 2, References: 25, Pages: 4
          Categories
          Original Research Article

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