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      GH/IGF-I Regulation in Obesity – Mechanisms and Practical Consequences in Children and Adults

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          Abstract

          Growth hormone (GH) secretion in children and adults is profoundly, but reversibly, suppressed in obesity. Since GH deficiency leads to increased fat mass, differentiation of both conditions remains challenging. Here we review the known and still speculative mechanisms underlying the inhibitory effects of obesity on GH secretion including peripheral factors like IGF-I and insulin, as well as central hypothalamic/pituitary modulators. We further discuss the basis of current testing for GH deficiency in obesity and the validity of the various provocative tests in overweight subjects.

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          Elevated plasma ghrelin levels in Prader Willi syndrome.

          Michael W. Schwartz, Molly E. Cummings, Karine Clément … (2002)
          Article 0 comments Cited 92 times – based on 0 reviews     Review now
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            Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men.

            G Lizarralde, A Iranmanesh, Raymond Veldhuis (1991)
            Mean plasma GH concentrations are controlled by the frequency, amplitude, and duration of underlying GH secretory bursts as well as by the half-life of endogenous GH. We investigated the specific mechanisms that subserve the clinically recognized negative effects of age and adiposity on mean serum GH concentrations. To this end, 21 healthy men, aged 21-71 yr, who were of nearly normal body weight underwent blood sampling at 10-min intervals for 24 h. Deconvolution analysis was used to estimate specific features of GH secretion and clearance. Compared to younger men, the older tertile of men had significant reductions in 1) GH secretory burst frequency, 2) the half-life of endogenous GH, and 3) the daily GH secretory rate, but not 4) GH secretory burst half-duration, amplitude, or mass. Linear regression analysis disclosed that age was a major negative statistical determinant of GH secretory burst frequency (r = -0.80; P = 0.005) and endogenous GH half-life (r = -0.70; P = 0.024). Body mass index, an indicator of relative obesity, was a significant negative correlate of GH half-life (P = 0.045) and GH secretory burst amplitude (P = 0.031). Age and body mass index each correlated negatively with the daily GH secretion rate (P = 0.0031 and P = 0.027, respectively), and together accounted for more than 60% of the variability in 24-h GH production rates (r = -0.78; P = 0.00056). On the average, for a normal body mass index, each decade of increasing age attenuated the GH production rate by 14% and the GH half-life by 6%. Conversely, each unit increase in body mass index, at a given age, reduced the daily GH secretion rate by 6%. We conclude that age and relative adiposity are distinct and specific correlates of individual attributes of GH secretion and clearance in men.
            Article 0 comments Cited 76 times – based on 0 reviews     Review now
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              Free insulin-like growth factors -- measurements and relationships to growth hormone secretion and glucose homeostasis.

              Jan Frystyk (2004)
              IGF-I is a multipotent growth factor with important actions on normal tissue growth and regeneration. In addition, IGF-I has been suggested to have beneficial effects on glucose homeostasis due to its glucose lowering and insulin sensitizing actions. However, not all effects of IGF-I are considered to be favorable; thus, epidemiological studies suggest that IGF-I is also involved in the development of common cancers, atherosclerosis and type 2 diabetes. The biological actions of IGF-I are modulated by at least six IGF-binding proteins, which bind approximately 99% of the circulating IGF-I pool. So far, most in vivo studies have used serum or plasma total (extractable IGF-I) as an estimate of the bioactivity of IGF-I in vivo. However, within the last decade, validated assays for measurement of free IGF-I have been described. This review aims to discuss the current assays for free IGF-I and their advances in relation to the traditional measurement of total IGF-I. The literature overview will focus on the role of circulating free versus total IGF-I in the feedback regulation of GH release, and the possible involvement of the circulating IGF-system in glucose homeostasis.
              Article 0 comments Cited 58 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (publisher-id): HRP
                Journal ID (nlm-ta): Horm Res Paediatr
                Journal ID (doi): 10.1159/issn.1663-2818
                Title: Hormone Research in Paediatrics
                Publisher: S. Karger AG
                ISSN (Print): 1663-2818
                ISSN (Electronic): 1663-2826
                Publication date Subscription-year: 2010
                Publication date (Print): March 2010
                Publication date (Electronic): 03 March 2010
                Volume: 73
                Issue: 3
                Pages: 153-160
                Affiliations
                aDepartment of Endocrinology, Christie Hospital, Manchester, UK; bDepartment of Neurosurgery, RWTH Aachen University, Aachen, Germany
                Article
                Publisher ID: 284355 Other ID: Horm Res Paediatr 2010;73:153–160
                DOI: 10.1159/000284355
                PubMed ID: 20197666
                SO-VID: 9011a4fd-ae7e-45bc-a49f-a3ecbf0d3d54
                Copyright © © 2010 S. Karger AG, Basel
                License:

                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
                Date received : 15 September 2009
                Date accepted : 12 October 2009
                Page count
                References: 78, Pages: 8
                Categories
                Subject: Mini Review

                ScienceOpen disciplines: Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Keywords: Growth hormone deficiency,Obesity,Growth hormone
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes, Neurology, Nutrition & Dietetics, Sexual medicine, Internal medicine, Pharmacology & Pharmaceutical medicine
                Keywords: Growth hormone deficiency, Obesity, Growth hormone

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