Growth hormone secretagogues (GHS) administered alone or in combination with growth hormone releasing hexapeptides, are effective probes for the diagnosis of GH deficiency in both children and adults. Current research has developed and tested different GHS compounds that are active by the oral route, and have improved potency and bioavailability, giving rise to exciting therapeutic possibilities. There was an enthusiastic response from experts in this area to the idea of distilling the huge amount of available data into one multi-authored volume. Each contributor has advanced the field of knowledge, and has here emphasized the practical aspects of their work, reviewing the subject in the light of their own experience. Therefore, the theme of the book is a practical one. The volume deals with all aspects of GHS that are relevant to the field, from the chemical structure to the different analogues, to the cloning and expression of the GHS-receptor and the role of these compounds in the physiological control of GH secretion. Also discussed are the most recent advances in relation to the possible role of these compounds in the diagnostic therapeutic settings in different clinical situations, either in children, adults or the elderly. The book meets the requirement of covering most, if not all of the advances in the field. It will enable scientists and clinicians to keep abreast of the rapidly evolving knowledge of the most recent years, and will also prove useful as a review for all interested in this topic.
Front Cover 1
Growth Hormone Secretagogues: Basic Findings and Clinical Implications 4
Copyright Page 5
Contents 8
Prologue 6
Contributing Authors 10
Chapter 1. Introduction 16
Chapter 2. GHRP: Unnatural Toward the Natural 20
Chapter 3. Impervious Peptides as GH Secretagogues 34
Chapter 4. GHRP Structure–Activity Relationship: An In Vivo Perspective 40
Chapter 5. Molecular Analysis of the Growth Hormone Secretagogue Receptor 50
Chapter 6. Intracellular GHRP Signalling 68
Chapter 7. The Effects of GH-Secretagogues on Human Pituitary Cells in Culture and on Rat Hypothalamic Tissue 80
Chapter 8. Hypothalamic Site and Mechanism of Action of Growth Hormone Secretagogues 94
Chapter 9. Mechanisms of Actions of Growth Hormone-Releasing Peptides and their Analogues In Vivo 106
Chapter 10. Animal Models of Growth Hormone Deficiency as Tools to Study Growth Hormone Releasing Mechanisms 120
Chapter 11. Regulation of Growth Hormone (GH) Pulsatility in Humans 130
Chapter 12. Hormonal Activities of Growth Hormone Secretagogues (GHS) Across Human Lifespan 154
Chapter 13. Effectiveness of Growth Hormone Secretagogues in the Diagnosis and Treatment of GH Secretory Deficiency 172
Chapter 14. Does Desensitisation to Growth Hormone Secretagogues Occur? 190
Chapter 15. GHRPs in Human Obesity 198
Chapter 16. Effects of Growth Hormone Secretagogues on in vivo Substrate Metabolism in Humans 210
Chapter 17. Growth Hormone Secretagogues. Physiological Role and Clinical Implications 224
Chapter 18. Growth Hormone Secretagogues in Critical Illness 240
Chapter 19. Growth Hormone Secretagogues in Catabolic Illness 252
Chapter 20. Treatment of Children with Short Stature by Growth Hormone Secretagogues 262
Chapter 21. Therapeutic Potential of GH Secretagogues in Adults 278
Chapter 22. Growth Hormone Secretagogue Influences Feeding Behaviour in Experimental Animals 294
Chapter 23. Growth Hormone Secretagogues and Sleep 300
Chapter 24. Hexarelin, A Synthetic Growth Hormone Secretagogue, Exhibits Protectant Activity in Experimental Myocardial lschemia and Reperfusion 316
Chapter 25. Potential Applications of Growth Hormone Secretagogues 330
Index 336
Contributing Authors
Erik F. Adams, Pharmaceutical Sciences Institute, Aston University, Birmingham, UK
Emanuela Arvat, Division of Endocrinology, University of Turin, 10126 Turin, Italy
Ariel L. Barkan, Professor of Medicine (Endocrinology and Metabolism) and Surgery (Neurosurgery), University of Michigan Medical Center, Division of Endocrinology and Metabolism, 3920 Taubman Center, Ann Arbor, MI 48109-0354, USA
Bengt-Åke Bengtsson, Research Centre for Endocrinology and Metabolism, Grӧna Stråket 8, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
Barry B. Bercu, Professor of Pediatrics, Pharmacology and Therapeutics, All Children’s Hospital, Department 6900, 801 Sixth Street South, St. Petersburg, FL 33701, USA
Ferruccio Berti, Department of Pharmacology, Chemiotherapy & Medical Toxicology, University of Milan, Via Vanvitelli, 32, 20129 Milan, Italy
Cyril Y. Bowers, Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112, USA
Nathalie Briard, Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 501, Faculté de Médecine, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
Fabio Broglio, Division of Endocrinology, University of Turin, 10126 Turin, Italy
Franco Camanni, Division of Endocrinology, University of Turin, 10126 Turin, Italy
Felipe F. Casanueva, Endocrinology Section, Dept. of Medicine, Santiago de Compostela University, P.O. Box 563, 15780 Santiago de Compostela, Spain
Chen Chen, Prince Henry’s Institute of Medical Research, P. O. Box 5152, Clayton, Victoria 3168, Australia
Jens Sandahl Christiansen, Institute of Experimental Clinical Research, University of Aarhus, and Medical Dep M (Endocrinology & Diabetes), Aarhus Kommunehospital, DK-8000 Aarhus, Denmark
Ross Clark, Research Centre for Developmental Medicine & Biology, School of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand
Iain J. Clarke, Prince Henry’s Institute of Medical Research, P. O. Box 5152, Clayton, Victoria 3168, Australia
Frédéric Dadoun, Service d’Endocrinologie, Maladies Métaboliques et de la Nutrition, Hôpital Nord, Chemin des Bourrely, 13915 Marseille Cedex 20, France, and Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 501, Faculté de Médecine, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
Vito De Gennaro Colonna, Dept. of Pharmacology, Chemiotherapy & Medical Toxicology, University of Milan, Via Vanvitelli, 32, 20129 Milan, Italy
Romano Deghenghi, Europeptides, Bt. Aristote, 9, Avenue du Marais, 95108 Argenteuil Cedex, France
Suzanne L Dickson, Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
Carlos Dieguez, Department of Physiology, Faculty of Medicine, University of Santiago de Compostela, Spain
Eleni V. Dimarki, Research Fellow, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0354, USA
Anne Dutour, Service d’Endocrinologie, Maladies Métaboliques et de la Nutrition, Hôpital Nord, Chemin des Bourrely, 13915 Marseille Cedex 20, France, and Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 501, Faculté de Médecine, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
Scott D. Feighner, Dept. of Metabolic Disorders, Merck Research Laboratories, Building RY-80-265, P.O. Box 2000, Rahway, NJ 07065, USA
Lawrence A. Frohman, Department of Medicine, University of Illinois at Chicago, 840 S. Wood Street (MC 787), Chicago, IL 60612, USA
Ricardo V. Garcia-Mayor, Internal Medicine, Hospital Xeral Cies, Vigo, Spain
Ezio Ghigo, Division of Endocrinology, University of Turin, Ospedale Molinette, C. Dogliotti 14, 10126 Turin, Italy
Roberta Giordano, Division of Endocrinology, University of Turin, 10126 Turin, Italy
Michel Grino, Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 501, Faculté de Médecine, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
Ashley B. Grossman, Department of Endocrinology, St Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, UK
Viviane Guillaume, Service d’Endocrinologie, Maladies Métaboliques et de la Nutrition, Hôpital Nord, Chemin des Bourrely, 13915 Marseille Cedex 20, France, and Laboratoire de Neuroendocrinologie Expérimentale, INSERM U 501, Faculté de Médecine, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
Andrew D. Howard, Dept. of Metabolic Disorders, Merck Research Laboratories, Building RY-80-265, P.O. Box 2000, Rahway, NJ 07065, USA
Donna L. Hreniuk, Dept. of Metabolic Disorders, Merck Research Laboratories, Building RY-80-265, P.O. Box 2000, Rahway, NJ 07065, USA
John-Olov Jansson, Research Centre for Endocrinology and Metabolism, Grӧna Stråket 8, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden
Richard C. Jenkins, Department of Medicine, University of Sheffield, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK
Rhonda D. Kineman, Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Márta Korbonits, Department of Endocrinology, St Bartholomew’s Hospital, West Smithfield, London EC1A 7BE, UK
Steven W.J. Lamberts, Professor of Medicine, Department of Medicine, University Hospital Dijkzigt, 40 Dr. Molewaterplein, 3015 GD Rotterdam, The Netherlands
Zvi Laron, Director, Endocrine & Diabetes Research Unit, Schneider Children’s Medical Center, 14 Kaplan Street, 49202 Petah Tikva, Israel
Alfonso Leal-Cerro, Endocrinology Unit, Hospital Virgen del Rocio, Seville, Spain
Mauro Maccario, Division of Endocrinology, University of Turin, 10126 Turin, Italy
Karen Kulju McKee, Dept. of Metabolic Disorders, Merck Research Laboratories, Building RY-80-265, P.O. Box 2000, Rahway, NJ 07065, USA
Shlomo Melmed, Academic Affairs, Cedars-Sinai Medical Center, 8700 Beverly Blvd., B-131, Los Angeles, CA 90048, USA
Dragan Micic, Institute of Endocrinology, University Clinical Center, Belgrade, Yugoslavia
Niels Møller, Institute of Experimental Clinical Research, University of Aarhus, and Medical Dep M (Endocrinology & Diabetes), Aarhus Kommunehospital, DK-8000 Aarhus, Denmark
Giampiero Muccioli, Division of Endocrinology, University of Turin, 10126 Turin, Italy
Ravi Nargund, Dept. of Medicinal Chemistry, Merck Research Laboratories, Building RY-80-265, P.O. Box 2000, Rahway, NJ 07065, USA
Ralf M. Nass,...
| Erscheint lt. Verlag | 7.9.1999 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizinische Fachgebiete ► Innere Medizin ► Endokrinologie |
| Medizinische Fachgebiete ► Innere Medizin ► Kardiologie / Angiologie | |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie | |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Biochemie | |
| Naturwissenschaften ► Biologie ► Humanbiologie | |
| Naturwissenschaften ► Biologie ► Zoologie | |
| ISBN-10 | 0-08-053269-1 / 0080532691 |
| ISBN-13 | 978-0-08-053269-1 / 9780080532691 |
| Haben Sie eine Frage zum Produkt? |
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