A Role for the Somatotropic Axis in Neural Development, Injury and Disease
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Arjan Scheepens
ABSTRACT
This review article discusses the roles of the somatotropic axis in the growth and development of the normal central nervous system (CNS) and during recovery from brain injury. Classically, the actions of pituitary-derived growth hormone (GH) have been reported to be primarily mediated via the induction of hepatic insulin-like growth factor-I (IGF-I). GH receptors (GHRs), however, have now been identified in many body tissues and shown to have both endocrine and local actions, some of which are IGF-I independent. Within the brain, GHRs are widely located across a range of cellular phenotypes, yet little is known regarding their function or endogenous ligand. It is now becoming accepted that GH, like IGF-I, is integrally involved in the growth and development of the normal CNS. Following brain injury, IGF-I mRNA is induced, primarily within reactive microglia. The resultant IGF-I protein appears to have a dual role, first as an endogenous neurotropic and anti-apoptotic agent acting directly on stressed cells, and second as a prohormone for generation of the N-terminal tripeptide of IGF-I, glycine-proline-glutamate (GPE), and the resulting des-N-(l-3)-IGF-I, both of which have specific neuroprotective properties. Our work on deciphering the upstream regulators of injury-induced IGF-I has revealed that a GH-like substance is strongly upregulated after brain injury and specifically associated with stressed neurons and glia. Subsequent to this finding, GH administered centrally 2 hours after a hypoxic-ischemic brain injury in juvenile rats was found to provide significant neuroprotection, interestingly, in a spatiotemporal pattern distinct from the neuroprotection offered by IGF-I. The implications of these findings in regard to the growth, development and injury response of the CNS are discussed.
© 2014 by Walter de Gruyter Berlin/Boston
Articles in the same Issue
- Titelei
- TABLE OF CONTENTS
- Foreword
- What Happens When Growth Hormone is Discontinued at Completion of Growth? Metabolic Aspects
- Growth Hormone Deficiency and Peak Bone Mass
- Optimal Strategy for Management of Pituitary Disease in the Growth Hormone-Deficient Teenager
- Ethical Dilemmas in Pediatric Endocrinology: Growth Hormone for Short Normal Children
- Evidence-Based Approach to Growth Hormone Replacement Therapy in Adults, with Special Emphasis on Body Composition
- Evidence-Based Growth Hormone Therapy Prediction Models
- New Paradigms for Growth Hormone Treatment in the 21st Century: Prediction Models
- Role of Insulin-like Growth Factor Monitoring in Optimizing Growth Hormone Therapy
- Knockout Mice Challenge Our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes Mellitus
- Type 2 Diabetes Mellitus in Children: Pathophysiology and Risk Factors
- Emergence of Type 2 Diabetes Mellitus in Children: Epidemiological Evidence
- Treatment of Type 2 Diabetes Mellitus in Children and Adolescents
- Diagnosis of Maturity-Onset Diabetes of the Young in the Pediatric Diabetes Clinic
- Thrifty Genotypes and Phenotypes in the Pathogenesis of Type 2 Diabetes Mellitus
- Estradiol: A Protective Factor in the Adult Brain
- Estrogen Treatment and Estrogen Suppression: Metabolic Effects in Adolescence
- Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom
- Route-Dependent Endocrine and Metabolic Effects of Estrogen Replacement Therapy
- Telomerase and the Cellular Lifespan: Implications for the Aging Process
- Human Aging and Progeria
- A Role for the Somatotropic Axis in Neural Development, Injury and Disease
- Hypothalamic Growth Hormone-Insulin-like Growth Factor-I Axis across the Human Life Span
- The Lost Voice: A History of the Castrato
- SELECTED POSTER ABSTRACTS
- GROWTH. FETAL GROWTH. SGA
- SYNDROMES: TURNER. PRADER-WILLI. NOONAN. PHP. OTHERS
- GHD. HYPOPITUITARISM. KIGS
- METABOLIC. GENETIC. ADULT. ACROMEGALY
- GH. IGF. IGFBPs
- GROWTH IN SYSTEMIC DISEASE. CRI. RICKETS. STEROIDS
Articles in the same Issue
- Titelei
- TABLE OF CONTENTS
- Foreword
- What Happens When Growth Hormone is Discontinued at Completion of Growth? Metabolic Aspects
- Growth Hormone Deficiency and Peak Bone Mass
- Optimal Strategy for Management of Pituitary Disease in the Growth Hormone-Deficient Teenager
- Ethical Dilemmas in Pediatric Endocrinology: Growth Hormone for Short Normal Children
- Evidence-Based Approach to Growth Hormone Replacement Therapy in Adults, with Special Emphasis on Body Composition
- Evidence-Based Growth Hormone Therapy Prediction Models
- New Paradigms for Growth Hormone Treatment in the 21st Century: Prediction Models
- Role of Insulin-like Growth Factor Monitoring in Optimizing Growth Hormone Therapy
- Knockout Mice Challenge Our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes Mellitus
- Type 2 Diabetes Mellitus in Children: Pathophysiology and Risk Factors
- Emergence of Type 2 Diabetes Mellitus in Children: Epidemiological Evidence
- Treatment of Type 2 Diabetes Mellitus in Children and Adolescents
- Diagnosis of Maturity-Onset Diabetes of the Young in the Pediatric Diabetes Clinic
- Thrifty Genotypes and Phenotypes in the Pathogenesis of Type 2 Diabetes Mellitus
- Estradiol: A Protective Factor in the Adult Brain
- Estrogen Treatment and Estrogen Suppression: Metabolic Effects in Adolescence
- Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom
- Route-Dependent Endocrine and Metabolic Effects of Estrogen Replacement Therapy
- Telomerase and the Cellular Lifespan: Implications for the Aging Process
- Human Aging and Progeria
- A Role for the Somatotropic Axis in Neural Development, Injury and Disease
- Hypothalamic Growth Hormone-Insulin-like Growth Factor-I Axis across the Human Life Span
- The Lost Voice: A History of the Castrato
- SELECTED POSTER ABSTRACTS
- GROWTH. FETAL GROWTH. SGA
- SYNDROMES: TURNER. PRADER-WILLI. NOONAN. PHP. OTHERS
- GHD. HYPOPITUITARISM. KIGS
- METABOLIC. GENETIC. ADULT. ACROMEGALY
- GH. IGF. IGFBPs
- GROWTH IN SYSTEMIC DISEASE. CRI. RICKETS. STEROIDS
