Table Of ContentSerono Symposia USA
Norwell, Massachusetts
PROCEEDINGS IN THE SERONO SYMPOSIA USA SERIES
THE SOMA TOTROPHIC AXIS AND THE REPRODUCTIVE PROCESS IN HEALTH
ANDDISEASE
Edited by Eli Y. Adashi and Michael O. Thorner
GHRH, GH, AND IGF-I: Basic and Clinical Advances
Edited by Marc R. Blackman, S. Mitchell Harman, Jesse Roth, and
Jay R. Shapiro
IMMUNOBJOLOGY OF REPRODUCTJON
Edited by Joan S. Hunt
FUNCTJON OF SOMA TIC CELLS IN THE TESTIS
Edited by Andrzej Bartke
GLYCOPROTEIN HORMONES: Structure, Function, and Clinical Implications
Edited by Joyce W. Lustbader, David Puett, and Raymond W. Ruddon
GROWTH HORMONE II: Basic and Clinical Aspects
Edited by Barry B. Bercu and Richard F. Walker
TROPHOBLAST CELLS: Pathways for Matemal-Embryonic Communication
Edited by Michae1 J. Soares, Stuart Handwerger, and Frank Talamantes
IN VITRO FERTILlZATION AND EMBRYO TRANSFER IN PRIMATES
Edited by Don P. Wolf, Richard L. Stouffer, and Robert M. Brenner
OVARIAN CELL INTERACTIONS: Genes to Physiology
Edited by Aaron J.W. Hsueh and David W. Schomberg
CELL BIOLOGY AND BIOTECHNOLOGY: Novel Approaches to Increased
Cellular Productivity
Edited by Melvin S. Oka and Randall G. Rupp
PREIMPLANTATJON EMBRYO DEVELOPMENT
Edited by Barry D. Bavister
MOLECULAR BASIS OF REPRODUCTIVE ENDOCRINOLOGY
Edited by Peter C.K. Leung, Aaron J.W. Hsueh, and Henry G. Friesen
MODES OF ACTJON OF GnRH AND GnRH ANALOGS
Edited by William F. CrowIey, Jr., and P. Michael Conn
FOLLlCLE STIMULA TING HORMONE: Regulation of Secretion and Molecular
Mechanisms of Action
Edited by Mary Hunzicker-Dunn and Neena B. Schwartz
SIGNALlNG MECHANISMS AND GENE EXPRESSJON IN THE OVARY
Edited by Geula Gibori
GROWTH FACTORS IN REPRODUCTJON
Edited by David W. Schomberg
Continued after Index
Serono Symposia USA
Norwell, Massachusetts
Mare R. Blaekman S. Mitehell Harman
Jesse Roth Jay R. Shapiro
Editors
GHRH, GH, and IGF-I
Basic and Clinical Advances
With 54 Figures
Springer Science+Business Media, LLC
Mare R. Blaekman, M.D. S. Mitehell Harman, M.D., Ph.D.
Division of Endoerinology and Metabolism Gerontology Researeh Center
Department of Medieine National Institute on Aging
Johns Hopkins University National Institutes of Health
Sehool of Medicine Baltimore, MD 21224
Baltimore, MD 21224 USA
USA
Jesse Roth, M.D. Jay R. Shapiro, M.D.
Division of Geriatrie Medicine and Division of Geriatrie Medieine and
Gerontology Gerontology
Department of Medicine Department of Medieine
Johns Hopkins University Johns Hopkins University
Sehool of Medicine Sehool of Medicine
Baltimore, MD 21224 Baltimore, MD 21224
USA USA
Proceedings of the Symposium on GHRH, GH, and IGF-I: Basic and C1inical Advances, sponsored by
Serono Symposia USA, Inc., held December 9 to 12, 1993, in San Diego, California.
For information on previous volumes, please contact Serono Symposia USA, lnc.
Library of Congress Cataloging-in-Publication Data
GHRH, GH, and IGF-I: basic and clinical advanceslMarc R. Blackman ... [et al.), editors.
p. cm.
Proceedings of the Symposium on GHRH, GH, and IGF-I: Basic and
Clinical Advances, sponsored by Serono Symposia USA, Inc., held
December 9 to 12, 1993, in San Diego, California" .. T.p. verso.
Includes bibliographical references and index.
ISBN 978-1-4612-6908-3 ISBN 978-1-4612-0807-5 (eBook)
DOI 10.1007/978-1-4612-0807-5
1. Somatotropin-Congresses. z. somatomedm-congresses.
3. Growth hormone releasing factor-Congresses. 1. Blackman, Marc
R. II. Serono Symposia, USA. III. Symposium on GHRH, GH, and
IGF-I: Basic and Clinical Advances (1993: San Diego, Calif.)
[DNLM: 1. Somatotropin-congresses. 2. Somatotropin-Releasing
Hormone-congresses. 3. Insulin-Like Growth Factor l-congresses.
4. Growth Disorders-therapy-congresses. WK 515 G427 1995)
QP572.S65G47 1995
612.6-dc20 94-36150
Printed on acid-free paper.
© 1995 Springer Science+Business Media New York
Originally published by Springer-Verlag New York, Ioc.in 1995
Softcover reprint oftiIe hardcover lst edition 1995
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ISBN 978-1-4612-6908-3
SYMPOSIUM ON GURU, GU, AND IGF-I:
BASIC AND CLINICAL ADVANCES
Scientific Committee
Marc R. Blackman, M.D., Chairman
Johns Hopkins University
Baltimore, Maryland
S. Mitchell Harman, M.D., Ph.D.
National Institutes ofHealth
Baltimore, Maryland
Jesse Roth, M.D.
Johns Hopkins University
Baltimore, Maryland
Jay R. Shapiro, M.D.
Johns Hopkins University
Baltimore, Maryland
Barry B. Bercu, M.D.
University ofSouth Florida
St. Petersburg, Florida
Shlomo Melmed, M.D.
Cedars-Sinai Medical Center
Los Angeles, California
Robert Marcus, M.D.
Veterans Affairs Medical Center
Palo Alto, California
Ron G. Rosenfeld, M.D.
Oregon Health Sciences University
Portland, Oregon
Organizing Secretaries
Bruce K. Burnett, Ph.D.
Leslie Nies
Serono Symposia USA, Inc.
100 Longwater Circle
Norwell, Massachusetts
•
Preface
Recent research suggests that adult growth hormone (GH) deficiency,
whether of pathological or physiological origin, is associated with a dis
tinct syndrome that includes alterations in body composition, endocrine
metabolic function, immune competence, and physical and psychosocial
well-being. Not surprisingly, substantial investigative effort is currently
focused on validating the above hypothesis and on determining whether
restoration of a normal GH-IGF-I axis in various states of adult GH
deficiency is clinically useful, safe, and cost-beneficial.
This book contains the proceedings from the Symposium on GHRH,
GH, and IGF-I: Basic and Clinical Advances, held December 9 to 12,
1993, in San Diego, California, and sponsored by Serono Symposia
USA, Inc. The conference was meant to highlight selected novel and
exciting clinical research developments related to possible therapeutic
uses of recombinant human GH and IGF-I, GHRH, GH releasing
peptides, and related GH secretagogues. This meeting occurred only one
year after a similar Serono symposium that was somewhat more oriented
to novel basic science discoveries, thus attesting to the current scientific
and clinical interest in this area.
The format of this volume follows that of the symposium and begins
with a scientific and clinical overview of the GHRH-somatostatin-GH
IGF-Iaxis. Contemporaryinsightsregardingthe physiology, biochemistry,
and molecular biology of hypothalamic-pituitary somatotrophic function
are discussed, as is the current understanding of GH and IGF-I receptors
and their binding proteins. This information forms the basis for sub
sequent presentations of clinical data from studies utilizing GH and/or
IGF-I in pediatric and adult patients with various catabolic conditions,
in patients with the syndrome of extreme resistance to GH (Laron
dwarfism), in children with non-GH-deficient short stature, and in non
elderly adults with pathological GH deficiency. Available data from the
studies in GH-deficient adults support the hypothesis that a distinct,
reversible GH-deficiency syndrome occurs in young and middle-aged
adults. This concept is further buttressed by detailed presentations of the
effects of GH and/or IGF-I administration on intermediary and bone
metabolism. The concluding segment posits the question whether age-
VlI
viii Preface
related decrements in GH and IGF-I, either in healthy or unhealthy
persons, define a syndrome like that described in younger adults with
pathological GH deficiency.
Throughout these discussions the authors emphasize (i) the distinction
between short-term pharmacological treatment and longer-term hormone
replacement therapy, with the attendant benefit/risk relationships; (ii) the
need to devisemorephysiologicalapproachesto treatmentandto quantify
biochemical and clinical GH and IGF-I status better before and after
therapeutic interventions; and (iii) the need to evaluate functionally
relevant physical, psychological, ethical, and economic outcome vari
ables. The closing, thought-provoking essay serves to temper the en
thusiasm of the unwary by challenging the too-rapid acceptance of the
concept that allstatesofGHdeficiency are pathological and by proffering
wise counsel regarding future, more selective approaches to therapeutic
investigations.
We thank the scientific committee, session chairs, speakers, and poster
presenters for their outstanding contributions to this symposium and for
their insightful, informative, and lively interchanges with the discussion
participants and other attendees. We are especially grateful to Leslie
Nies, her superb staff at Serono Symposia USA, Inc., and Dr. Bruce
Burnett for their unflagging assistance with the organization of this
symposium, for generously providing funds to enable trainees and young
investigators to attend this conference, and for their patience throughout
the editorial process of this book. We thank the contributors to this
volume and hope that their work will stimulate further research into this
exciting field.
MARC R. BLACKMAN
S. MITCHELL HARMAN
JESSE ROTH
JAY R. SHAPIRO
•
Contents
Preface vii
Contributors xiii
PartI. OverviewofPhysiology ofthe
GHRH-Somatostatin-GH-IGF-IAxis
1. Physiologyofthe Growth Hormone Releasing
Hormone-Somatostatin-GrowthHormone-Insulin-Like
Growth Factor I Axis 3
LAWRENCE A. FROHMAN
2. Role ofSomatostatin in the Regulation of
Growth Hormone Secretion 11
SEYMOURREICHLIN
3. Growth Hormone Releasing Hormone and Growth Hormone
ReleasingPeptides 19
MARY LEEVANCE, JOSEPH A. ALOI, MARKL. HARTMAN,
SUSAN E. KIRK, AND MICHAEL O. THORNER
4. GHBindingProtein, GH Receptors, and DomainsInvolved
in SignalTransduction 25
P.A. KELLY, J. FINIDORI, M.-C. POSTEL-VINAY, M. EDERY,
L. GOUJON, A. SOTIROPOULOS, H. DINERSTEIN,
AND J.-J. LEBRUN
5. Insulin-Like Growth FactorsDuring Development. ........ 38
DEREKLEROITH, STEFAN NEUENSCHWANDER, ANTOLII KOVAL,
CHARYSESINDLER, AND CHARLEST. ROBERTS, JR.
ix
x Contents
PartII. EffectsofRecombinant Human GHand/or IGF-Iin
CatabolicIllness
6. AnabolicEffects ofRecombinant Human Growth Hormone
and Insulin-Like Growth FactorI in HumanDisease 51
RAYMONDL. HINTZ
7. Growth Hormonein Children with ChronicRenal Disease:
Some Metabolic Considerations 56
D.F. GEARY AND K. WELCH
8. Growth Hormone: TheVisible Difference in Burn Care 61
MICHAELJ. MULLER, THOMAS C. RUTAN,
ANDDAVID N. HERNDON
9. EffectsofRecombinant Human Growth Hormone on Body
Composition and Metabolism in HIV-AssociatedWasting 75
K. MULLIGAN, C. GRUNFELD, M.K. HELLERSTEIN,
R.A. NEESE, AND M. SCHAMBELAN
10. Administration ofGrowth Hormone as an Adjunct to
Nutritional Support in Critical Illness 91
THOMAS R. ZIEGLER
11. Strategiesfor the Use ofRecombinant Human Growth
Hormone and Insulin-Like Growth FactorI in
AmyotrophicLateral Sclerosis 110
BARRYW. FESTOFF, SHI X. YANG, AND DAVID STONG
PartIII. Contemporary IssuesinGrowth and Development
12. ContemporaryIssuesin Growth and Development:
An Overview 131
GEORGE A. WERTHER
13. UseofRecombinantIGF-I in Syndromes of
GHInsensitivity 136
RON G. ROSENFELD, ARLAN L. ROSENBLOOM,
AND JAIME GUEVARA-AGUIRRE
14. UseofGrowth Hormone in Non-Growth-Hormone-Deficient
Children: Physiologic, Pharmacologic, and EthicalIssues ... 143
BARRyB.BERCU,HOWARDJ. HEINZE,ANDRICHARDF.WALKER
Contents xi
15. Growth HormoneTreatmentofNonelderly Adults
with GH Deficiency 169
JENS S. CHRISTIANSEN, JENS O.L. J0RGENSEN,
NINA VAHL, ANDERS JUUL, J0RN MULLER, AND
NIELS E. SKAKKEBiEK
PartIV. EffectsofrhGHand IGF-Ion
Intermediaryand BoneMetabolism
16. OverviewofGrowth Hormone and IGF-I Effectson
IntermediaryMetabolism and Bone ...................... 179
SHLOMOMELMED
17. EffectsofrhGH on Glucose, Lipid, and
Amino Acid Metabolism 185
KENNETH C. COPELANDAND K. SREEKUMARUN NAIR
18. MetabolicEffects ofIGF-I: Implicationsfor the Therapyof
DiabetesMellitus 195
ROBERTS. SHERWIN, WALTER P. BORG,
ANDSUSAN D. BOULWARE
19. Modulation ofResponses to GHand IGF-I by
Nutritional Variables 204
DAVID K. SNYDER
20. Growth Hormone Effects on the Adult Skeleton. .......... 217
ROBERTMARCUS
21. Insulin-Like Growth Factorsand Skeletal Remodeling 222
JULIE PATTERSON, JAY R. SHAPIRO, AND MARC R. BLACKMAN
PartV. UseofGHRH, rhGH, and rhIGF-I in Aging
22. Growth Hormone and Aging: A BriefReview. ............ 233
S. MITCHELLHARMAN AND MARC R. BLACKMAN
23. PotentialBenefits and Risks inTreating
the Hyposomatomedinemia and Hypogonadism
ofElderly Men 241
DANIELRUDMAN AND KAUP R. SHETTY
