Ghrelin
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Table of contents
- Contentsvii
- Former Editorsv
- Contributorsxiii
- Prefacexvii
- Chapter 1: The Structure of Ghrelin1
- I. Introduction2
- II. Background2
- A. Experimental methods2
- B. Computational methods4
- III. Results of Structural Studies5
- A. Nuclear magnetic resonance5
- B. MD simulations6
- IV. Discussion9
- V. Conclusions11
- Acknowledgments11
- References11
- Chapter 2: Biochemistry of Ghrelin Precursor Peptides13
- I. Introduction14
- II. Ghrelin Gene Precursors15
- A. Organization of the ghrelin gene15
- B. Promoter activity15
- III. Posttranslational Products of Proghrelin17
- A. Ghrelin and desacyl ghrelin17
- B. C-ghrelin peptides20
- IV. Distribution of Proghrelin Peptides22
- V. Proghrelin Peptides in Lower Vertebrates24
- VI. Summary25
- References25
- Chapter 3: Structure of Mammalian and Nonmammalian Ghrelins31
- I. Introduction32
- II. Mammalian Ghrelin33
- A. Molecular forms of ghrelin in rat stomach33
- B. Multiple forms of ghrelin in human stomach34
- C. Molecular forms of ghrelin in several tissues35
- D. Other mammalian ghrelin35
- III. Nonmammalian Ghrelin36
- A. Bird ghrelin36
- B. Fish ghrelins37
- C. Frog ghrelin39
- D. Reptile ghrelin40
- IV. Ghrelin and Motilin Family40
- V. Activity Change by Fatty Acid Chain Length of Ghrelin41
- VI. Putative Ghrelin Acyl-Modifying Enzyme41
- VII. Conclusion43
- References43
- Chapter 4: The Growth Hormone Secretagogue Receptor47
- I. Introduction: A Case of Reverse Pharmacology48
- II. Genetics and Molecular Biology49
- A. The GHSR gene49
- B. Structure of GHSR1a52
- III. Regulation of Gene Expression55
- A. Promoter sequences55
- B. Hormonal regulation56
- C. Ligand-independent activity57
- IV. Signal Transduction58
- A. Pathways leading to GH secretion58
- B. Other signaling systems61
- V. GHSR1a: Tissue Distribution and Functions in Different Organ Systems62
- A. The hypothalamic-pituitary axis and energy balance62
- B. Energy balance64
- C. Immune system modulation and anti-inflammatory properties of ghrelin67
- D. Ghrelin, GHSR, and aging71
- E. Expression and effects in other tissues74
- VI. Other Ligands74
- A. Alternative forms of ghrelin74
- B. Adenosine75
- C. Cortistatin77
- VII. Evidence for Other Receptors77
- VIII. Future Directions78
- References79
- Chapter 5: Basic Aspects of Ghrelin Action89
- I. Introduction90
- II. Structure of GHSR1a: A G-Protein–Coupled Receptor91
- III. How to Define the Role of the System Ghrelin/GHSR1a?96
- IV. Are There Alternative Ligands for the GHSR1a?97
- V. Endocytosis of GHSR1a98
- VI. Homo- or Heteromeric Complexes for GHSR1a99
- VII. GHSR1a: G-Protein-Signaling Pathways101
- VIII. A Brief Commentary: ‘‘New’’ Receptors for Ghrelin and Desacyl Ghrelin107
- IX. Concluding Remarks108
- Acknowledgments109
- References109
- Chapter 6: Appetite and Metabolic Effects of Ghrelin and Cannabinoids: Involvement of AMP-Activated121
- I. Introduction122
- II. Ghrelin122
- A. Function122
- B. Appetite effects123
- C. Metabolic effects125
- D. Effects on cardiovascular system126
- III. Cannabinoids127
- A. Function127
- B. Appetite effects128
- C. Metabolic effects129
- D. Effects on cardiovascular system130
- IV. Adenosine Monophosphate-Activated Protein Kinase131
- A. Structure131
- B. Role on appetite133
- C. Role on peripheral metabolism: Glucose and lipids133
- D. Role on cardiovascular function134
- V. The Effects of Ghrelin and Cannabinoids on AMPK135
- A. Human studies with rimonabant137
- References138
- Chapter 7: Ghrelin and Feedback Systems149
- I. Introduction150
- II. Regulation of Ghrelin Secretion151
- A. Starvation and feeding151
- B. Efferent vagus nerve152
- C. Body weight152
- D. Hormones and peptides153
- E. Brain neurotransmitters157
- F. Gastric bypass158
- III. Afferent Pathways of Ghrelin from the Stomach to the Hypothalamus158
- IV. Hyperphagia, Obesity, and Des-acyl Ghrelin159
- V. Hypothalamic Gene Expression and Plasma Des-acyl Ghrelin161
- VI. Conclusion161
- Acknowledgments162
- References162
- Chapter 8: Ghrelin Gene-Related Peptides Modulate Rat White Adiposity171
- I. Introduction172
- II. Effects of Ghrelin on Rat Retroperitoneal Adipocyte Endocrine Functions176
- A. Animals176
- B. RP adipocyte isolation176
- C. Set up of the adipocyte culture system for evaluation of the leptin-releasing activity of ghrelin177
- D. Adipocyte RNA isolation and analyses177
- E. Leptin measurement178
- F. RP adipocyte endocrine function179
- III. Desacyl Ghrelin as a Potential Physiological Modulator of Adiposity183
- A. Isolation and differentiation of RP preadipocytes184
- B. Determination of glucose concentration in culture medium185
- C. RT-PCR analysis186
- IV. Discussion and Remarks193
- Acknowledgments199
- References199
- Chapter 9: Cardiac, Skeletal, and Smooth Muscle Regulation by Ghrelin207
- I. Introduction208
- II. Structure and Distribution of Ghrelin210
- A. Structure210
- B. Distribution210
- C. Receptors214
- III. Contractile Effects of Ghrelin217
- A. Myocardium217
- B. Smooth muscle223
- C. Skeletal muscle227
- Acknowledgments230
- References230
- Chapter 10: Ghrelin and Bone239
- I. Bone Balance: Resorption and Formation239
- II. Interplay Between the Gastrointestinal System and Bone: The Effect of Gastrectomy/Fundectomy on240
- III. Effects of GH and GHS on Bone Metabolism242
- IV. Correlation Between Ghrelin and Bone Parameters in Clinical Studies244
- V. Effects of Ghrelin on Osteoblastic Cells In Vitro245
- VI. Conclusions249
- References249
- Chapter 11: Ghrelin in Pregnancy and Lactation259
- I. Introduction260
- II. GHSRs in Pregnancy260
- III. Ghrelin in the Fallopian Tubes, Uterus, and Placenta262
- IV. Ghrelin Secretion in Pregnancy262
- A. Diurnal profile: Effect of meals, sleep, and tobacco264
- B. Ghrelin secretion at delivery264
- V. Placenta as a Source of Ghrelin?265
- VI. Physiological Actions of Ghrelin in Pregnancy266
- A. Appetite and adipose tissue metabolism266
- B. Hyperinsulinemia and insulin resistance268
- C. Ghrelin and the GH axis268
- D. Hypertensive disorders: Preeclampsia271
- E. Direct effects of maternal ghrelin levels on the fetus272
- F. Birth272
- G. Other effects272
- VII. Lactation273
- VIII. Fetal Ghrelin274
- A. Fetal ghrelin and fetal and neonatal growth275
- IX. Future Directions for Research276
- X. Summary276
- Acknowledgments277
- References277
- Chapter 12: Ghrelin and Reproduction: Ghrelin as Novel Regulator of the Gonadotropic Axis285
- I. Introduction: Ghrelin Is a Multifunctional Regulator with Key Roles in Energy Balance286
- II. Neuroendocrine Control of Reproduction: The Gonadotropic Axis287
- III. Reproduction and the Energy Status Are Functionally Linked288
- IV. Ghrelin as Putative Regulator of the Gonadotropic Axis289
- V. Role of Ghrelin in the Control of Gonadotropin Secretion289
- VI. Putative Roles of Ghrelin in Puberty Onset291
- VII. Molecular Diversity of Ghrelin: Reproductive Effects of UAG and Obestatin292
- VIII. Expression and Direct Actions of Ghrelin in the Gonads293
- IX. Futures Perspectives and Conclusions295
- Acknowledgments297
- References298
- Chapter 13: Ghrelin and Prostate Cancer301
- I. Prostate Cancer302
- II. Influences of Hormones on Prostate Cancer Progression303
- III. The Peptide Hormone Ghrelin and Prostate Cancer307
- A. The many faces of the ghrelin biology307
- B. Effects on cell growth311
- C. Ghrelin and its receptors in human prostate tumors and related cell lines312
- D. Functional role of ghrelin in prostate cancer314
- IV. Conclusions315
- Acknowledgments316
- References316
- Chapter 14: Novel Connections Between the Neuroendocrine and Immune Systems: The Ghrelin Immunoregul325
- I. Neuroendocrine–Immune Interactions326
- II. The Growth Hormone Secretagogue Receptor327
- A. Growth hormone secretagogues327
- B. GHSR properties328
- C. GHSR expression on immune cells328
- III. Ghrelin: Hormone or Cytokine?329
- A. Properties of ghrelin329
- B. Sources of ghrelin production330
- C. Biological and functional activities of ghrelin332
- IV. Conclusions341
- Acknowledgments342
- References342
- Index347
First published in 1943, VITAMINS AND HORMONES is the longest-running serial published by Academic Press. In the early days of the Serial, the subjects of vitamins and hormones were quite distinct. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms.
Under the capable and qualified editorial leadership of Dr. Gerald Litwack, VITAMINS AND HORMONES continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines.
Under the capable and qualified editorial leadership of Dr. Gerald Litwack, VITAMINS AND HORMONES continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines.