The Somatotrophic Axis in Brain Function

1st Edition - November 22, 2005
Editor: Fred Nyberg
Language: English
eBook ISBN:
9 7 8 - 0 - 0 8 - 0 4 9 8 1 6 - 4

The somatotropic axis is one of the major hormonal systems regulating postnatal growth in mammals. It interacts with the central nervous system on several levels. Growth hormone… Read more

The Somatotrophic Axis in Brain Function

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The somatotropic axis is one of the major hormonal systems regulating postnatal growth in mammals. It interacts with the central nervous system on several levels. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) receptors are expressed in many brain areas including the hippocampus, pituitary and hypothalamus. GH and IGF-I are important factors in the development and differentiation of the CNS and have protective properties in dementia, as well as in traumatic and ischaemic injury of the CNS. Also GH has an important impact on mood and well-being with GH secretory capacity being reduced in depression.This volume will include chapters (1) on basic knowledge on GH/IGF-1, (2) on localization of GH/IGF-1 and their receptors in the CNS, including blood brain barrier transport of both hormones, (3) on actions of the two hormones on CNS function (basic science), (4) on clinical aspects of GH/IGF-1 in relation to various CNS functions and disorders, and finally (5) on some future perspectives in this area of science.

Preface
Pioneers in the growth hormone field
Section 1: Biosynthesis of Growth Hormone and Insulin-like Growth Factor-I and Regulation of Their Secretion
- Introduction
- Chapter 1: Regulation and Mechanism of Growth Hormone and Insulin-like Growth Factor-I Biosynthesis and Secretion
  - Publisher Summary
  - I INTRODUCTION
  - II GROWTH HORMONE
  - III INSULIN-LIKE GROWTH FACTOR-I
  - IV FUTURE PERSPECTIVES
- Chapter 2: Ghrelin, an Endogenous Ligand for the Growth Hormone Secretagogue Receptor
  - Publisher Summary
  - I INTRODUCTION
  - II GROWTH HORMONE SECRETAGOGUE AND ITS RECEPTOR
  - III PURIFICATION AND IDENTIFICATION OF GHRELIN
  - IV DISTRIBUTION OF GHRELIN
  - V PHYSIOLOGICAL FUNCTIONS OF GHRELIN
  - VI GHRELIN KNOCKOUT MOUSE
  - VII GHRELIN RECEPTOR KNOCKOUT MOUSE
  - VIII REGULATION OF GHRELIN SECRETION
  - IX EPILOGUE
  - Acknowledgments
Section 2: Growth Hormone and Insulin-like Growth Factor-I and their Function at the Receptor Level
- Chapter 3: Mechanisms of Signal Transduction Utilized by Growth Hormone
  - Publisher Summary
  - I INTRODUCTION
  - II THE GROWTH HORMONE RECEPTOR
  - III SIGNAL TRANSDUCTION PATHWAYS ACTIVATED BY GROWTH HORMONE
  - IV CONCLUSION
- Chapter 4: Insulin-like Growth Factor-I and Its Binding Proteins: Regulation of Secretion and Mechanism of Action at the Receptor Level
  - Publisher Summary
  - 1 INTRODUCTION AND OVERVIEW
  - II OVERVIEW OF INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS
  - II SUMMARY AND FUTURE PERSPECTIVE
  - Acknowledgments
Section 3: Growth Hormone and Insulin-like Growth Factors and Their Receptors in the Central Nervous System
- Chapter 5: Growth Hormone and Insulin-like Growth Factor-I in Human Cerebrospinal Fluid
  - Publisher Summary
  - I INTRODUCTION
  - II GROWTH HORMONE AND INSULIN-LIKE GROWTH FACTOR-I (IGF-I) IN THE CEREBROSPINAL FLUID (CSF) COMPARTMENT
  - III RELATIONS BETWEEN CSF DETECTABLE LEVELS OF GROWTH HORMONE AND IGF-I TO VARIOUS PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL CONDITIONS
  - IV FUTURE PERSPECTIVES
  - Acknowledgment
- Chapter 6: Growth Hormone, Insulin, and Insulin-like Growth Factor-I: Do They Interact at the Blood-Brain Barrier?
  - Publisher Summary
  - I WHY THERE IS AN ISSUE ABOUT WHETHER GROWTH HORMONE (GH) CROSSES THE BLOOD–BRAIN BARRIER (BBB)
  - II CURRENT KNOWLEDGE ABOUT THE TRANSPORT SYSTEMS FOR INSULIN AND INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AT THE BBB
  - III ABSENCE OF A SATURABLE TRANSPORT SYSTEM FOR GH AT THE BBB
  - IV LACK OF DIRECT INTERACTION OF GH AND INSULIN AT THE BBB, BUT IGF-I MAY BE AN INDIRECT MEDIATOR
  - V CONCLUSIONS
  - Acknowledgment
- Chapter 7: Growth Hormone and Insulin-like Growth Factors in the Central Nervous System: Localization in Mammalian Species
  - Publisher Summary
  - I EXPRESSION OF THE GROWTH HORMONE SYSTEM IN THE MAMMALIAN BRAIN
  - II EXPRESSION OF THE IGF SYSTEM IN THE BRAIN
- Chapter 8: Purification of Growth Hormone Receptors from Human Brain Tissues
  - Publisher Summary
  - I INTRODUCTION
  - II METHODS FOR PURIFICATION
  - III CHARACTERISTICS OF HIGHLY AND PARTLY PURIFIED GROWTH HORMONE (GH) RECEPTORS
  - IV CONCLUSION
  - Acknowledgment
- Chapter 9: Growth Hormone Receptor Message in the Rat and Human Central Nervous System: Structure and Function
  - Publisher Summary
  - I INTRODUCTION
  - II CLONING OF THE GROWTH HORMONE RECEPTOR (GHR)
  - III GROWTH HORMONE-BINDING PROTEIN
  - IV GHR mRNA IN THE CENTRAL NERVOUS SYSTEM (CNS)
  - V REGULATION OF GHR GENE EXPRESSION
  - Acknowledgment
Section 4: Central Nervous System Action of Growth Hormone: Basic Studies Using Animal Models
- Chapter 10: Interaction of Growth Hormone and Prolactin in Brain Circuits
  - Publisher Summary
  - I INTRODUCTION
  - II COMMON FEATURES OF THE SOMATOTROPHIC AND LACTOTROPHIC SYSTEMS IN THE CENTRAL NERVOUS SYSTEM
  - III DIFFERENTIAL ACTIONS OF GROWTH HORMONE AND PROLACTIN IN THE BRAIN
  - IV POTENTIAL INTERACTION OF THE TWO HORMONES IN BRAIN FUNCTION
  - V CONCLUSION
- Chapter 11: Growth Hormone and Insulin-like Growth Factor-I and Cellular Regeneration in the Adult Brain
  - Publisher Summary
  - I INTRODUCTION
  - II NEUROPROTECTIVE ACTIONS OF THE SOMATOTROPHIC AXIS
  - III MODELS AND TECHNIQUES
  - IV ADULT CELL GENESIS BY INSULIN-LIKE FACTOR-I AND GROWTH HORMONE
  - V PHYSIOLOGICAL AND FUNCTIONAL CORRELATES TO ADULT CELL GENESIS
- Chapter 12: Growth Hormone and Insulin-like Growth Factor-I and Their Effects on Astroglial Gap Junctions
  - Publisher Summary
  - I GAP JUNCTIONS AND CONNEXINS IN THE CENTRAL NERVOUS SYSTEM (CNS)
  - II ASTROCYTES IN THE CNS
  - III GROWTH HORMONE (GH) AND INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND ASTROCYTES AND CONNEXIN43 – GAP JUNCTIONS
  - IV METHODOLOGICAL ASPECTS
  - V SIGNIFICANCE OF REGULATION OF CONNEXIN43 AND GAP JUNCTIONAL COUPLING
  - VI REGULATION OF CONNEXIN43 BY GH AND IGF-I IN THE CONTEXT OF OTHER EFFECTS
  - VII GAP JUNCTIONAL PLASTICITY AND CORTICAL FUNCTIONS
- Chapter 13: Rodent Models for the Study of the Role of Growth Hormone–Insulin-like Growth Factor-I or the Insulin Axis in Aging and Longevity: Special Reference to a Transgenic Dwarf Rat Strain and Calorie Restriction
  - Publisher Summary
  - I INTRODUCTION
  - II LONGEVITY MODELS FOR THE GROWTH HORMONE–INSULIN-LIKE GROWTH FACTOR-I/INSULIN AXIS
  - III THE GLUCOSE–INSULIN SYSTEM
  - IV STRESS RESPONSE
  - V CONCLUSION
- Chapter 14: Growth Hormone and Insulin-like Growth Factor-I and Their Interactions with Brain Circuits Involved in Cognitive Function
  - Publisher Summary
  - I INTRODUCTION
  - II THE GROWTH HORMONE/INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AXIS
  - III ACTIONS OF GROWTH HORMONE AND IGF-I IN THE MAMMALIAN BRAIN
  - IV GROWTH HORMONE/IGF-I AXIS AND BRAIN AGING
  - V SUMMARY
- Chapter 15: Insulin-like Growth Factor-I and Neuroprotection
  - Publisher Summary
  - I INTRODUCTION
  - II NEUROPROTECTIVE SIGNALING
  - III INSULIN-LIKE GROWTH FACTOR-I (IGF-I) REGULATES NEW BRAIN CELL POPULATIONS
  - IV IGF-I MAINTAINS BRAIN CELL FUNCTION
  - V MECHANISMS OF NEUROPROTECTION BY IGF-I
  - VI LOSS OF IGF-I FUNCTION CONTRIBUTES TO BRAIN AGING AND DISEASE
  - VII PERSPECTIVES
  - Acknowledgment
Section 5: Immediate and Long-Term Benefits on the Central Nervous System and Growth Hormone Replacement Therapy
- Chapter 16: Quality of Life in Adult Growth Hormone Deficiency
  - Publisher Summary
  - I INTRODUCTION
  - II WHY IS QUALITY OF LIFE (QoL) IMPORTANT?
  - III WHAT DO WE MEAN BY “QUALITY OF LIFE?”
  - IV MEASUREMENT OF QUALITY OF LIFE
  - V EFFECT OF UNTREATED GROWTH HORMONE (GH) DEFICIENCY (GHD) ON QUALITY OF LIFE
  - VI IS GH CAUSATIVE IN THE IMPAIRED QoL OF HYPOPITUITARY ADULTS?
  - VII QoL FOLLOWING DISCONTINUATION OF CHILDHOOD GH THERAPY
  - VIII NATURAL HISTORY OF QoL IN ADULTS WITH UNTREATED GHD
  - IX EFFECTS OF GH REPLACEMENT ON QoL IN GHD HYPOPITUITARY ADULTS
  - X SPECIFIC PATIENT GROUPS
  - XI EFFECT OF LONG-TERM GH REPLACEMENT ON QoL
  - XII PREDICTORS OF IMPROVEMENTS IN QoL WITH GH REPLACEMENT
  - XIII POTENTIAL BIASES IN OPEN STUDIES OF QoL
  - XIV SUMMARY
- Chapter 17: The Somatotropic Axis in Psychologic Functioning: Effects on Sleep and Psychopathology
  - Publisher Summary
  - I INTRODUCTION
  - II SLEEP
  - III MOOD AND PSYCHIATRIC SYMPTOMS
- Chapter 18: Growth Hormone Replacement Therapy in Adults: Responsiveness Related to Life Quality
  - Publisher Summary
  - I INTRODUCTION
  - II QUALITY OF LIFE (QoL) MEASUREMENTS
  - III QoL IN GROWTH HORMONE (GH)-DEFICIENT ADULTS
  - IV EFFECTS OF GH DEFICIENCY AND GH THERAPY ON QoL IN SPECIFIC CONDITIONS
  - V THERAPEUTIC MECHANISMS OF GH REPLACEMENT
  - VI COST–BENEFIT CONSIDERATIONS
  - VII CONCLUSION
- Chapter 19: Psychological Importance to the Child of Growth Hormone Replacement
  - Publisher Summary
  - I INTRODUCTION
  - II MODES OF ACTION OF GROWTH HORMONE (GH)
  - III LOCATION OF ACTION OF GH
  - IV GH SECRETION VERSUS SENSITIVITY
  - V TYPICAL COGNITIVE DEVELOPMENT AND CRITICAL WINDOWS OF DEVELOPMENT
  - VI EFFECT OF GH ON COGNITIVE AND ACADEMIC PERFORMANCE
  - VII EFFECT OF GH ON PSYCHOLOGICAL WELL-BEING
  - VIII METHODOLOGICAL DIFFICULTIES IN MEASUREMENT
  - IX FUTURE DIRECTIONS
- Chapter 20: Acromegaly and Brain Function: Effects on the Human Brain during Conditions with Increased Growth Hormone Concentrations
  - Publisher Summary
  - I BRAIN EFFECTS DURING GROWTH HORMONE HYPERSECRETION
  - II TREATMENT OF GROWTH HORMONE-PRODUCING TUMORS
- Chapter 21: Human Aging and the Growth Hormone/Insulin-like Growth Factor-I Axis: The Impact of Growth Factors on Dementia
  - Publisher Summary
  - I INTRODUCTION
  - II AGE-RELATED CHANGES IN ACTIVITY OF THE GROWTH HORMONE (GH)/INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AXIS: FOCUS ON NORMAL AGING
  - III GH/IGF-I AXIS IN DEMENTIA: FOCUS ON ALZHEIMER’S DISEASE
  - IV GH/IGF-I AXIS IN DOWN SYNDROME: A CLINICAL MODEL OF ANTICIPATED AGING OF THE GH/IGF/I AXIS
  - V CONCLUSIONS
- Chapter 22: Cognitive Status of Adult Growth Hormone (GH)-Deficient Patients and GH-Induced Neuropsychological Changes
  - Publisher Summary
  - I INTRODUCTION
  - II DETERMINATION OF THE ROLE OF GROWTH HORMONE (GH) IN COGNITIVE FUNCTIONS
  - III COGNITIVE EFFECTS OF GH-INDUCED HORMONAL CHANGES
  - IV COGNITIVE STATUS IN RELATION TO GH DEFICIENCY (GHD) AND GH TREATMENT
  - V META-ANALYSIS GH AND NEUROPSYCHOLOGICAL FUNCTIONS
  - VI COGNITIVE EFFECTS OF DISCONTINUED GH TREATMENT
  - VII GH DOSAGES AND COGNITIVE STATUS IN GH-DEFICIENT ADULTS
  - VIII GH AND INSULIN-LIKE GROWTH FACTOR I REPLACEMENT IN SYNDROMES OTHER THAN GHD
  - IX GH-INDUCED COGNITIVE CHANGES IN HEALTHY ELDERLY SUBJECTS
  - X CONCLUSION
- Chapter 23: Growth Hormone and Insulin-like Growth Factor-I in Alzheimer’s Disease
  - Publisher Summary
  - I INTRODUCTION
  - II GROWTH HORMONE AND INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND COGNITIVE DECLINE IN THE ELDERLY
  - III INTERACTIONS BETWEEN IGF-I SYSTEM AND ALZHEIMER’S DISEASE
  - IV GROWTH HORMONE IN ALZHEIMER’S DISEASE
  - V GROWTH HORMONE RESPONSE IN ALZHEIMER’S DISEASE
  - VI SOMATOSTATIN IN CEREBROSPINAL FLUID IN ALZHEIMER’S DISEASE
  - VII RELATIONSHIP BETWEEN ALZHEIMER’S DISEASE TREATMENT AND IGF-I SYSTEM AND GROWTH HORMONE RESPONSE TO STIMULI
  - VIII POSSIBLE USEFULNESS OF GROWTH HORMONE/IGF-I AXIS IN ALZHEIMER’S DISEASE TREATMENT
Section 6: Growth Hormone Replacement and Related Therapies in Central Nervous System Disorders: A Future Perspective
- Chapter 24: Growth Hormone Antagonists: A Pharmacological Tool in Present and Future Therapies
  - Publisher Summary
  - 1 INTRODUCTION
  - II THE DISCOVERY OF GROWTH HORMONE ANTAGONISTS
  - III DEVELOPMENT OF PEGVISOMANT
  - IV PRECLINICAL TRIALS
  - V CLINICAL TRIALS
  - VI OTHER USES OF PEGVISOMANT
  - VII CONCLUSION
  - Acknowledgments
- Chapter 25: Growth Hormone Replacement Therapy and Life Quality: Future Perspectives
  - Publisher Summary
  - I CASE STUDY: NEUROPROTECTIVE EFFECT OF GROWTH HORMONE IN SPINAL CORD INJURY
  - II GROWTH HORMONE REPLACEMENT AND LIFE QUALITY IN THE FRAIL ELDERLY
  - III GROWTH HORMONE REPLACEMENT AND QUALITY OF LIFE IN ADULTS WITH GROWTH HORMONE DEFICIENCY
Index

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Fred Nyberg