Reproductive Endocrinology (eBook)
XVI, 361 Seiten
Springer US (Verlag)
978-0-387-88186-7 (ISBN)
Molecular biology emerged from advances in biochemistry during the 1940s and 1950s, when the structure of the nucleic acids and proteins were elucidated. Beginning in the 1970s, with nucleic acid enzymology and the discovery of the restriction enzymes, the tools of molecular biology became widely available and applied in cell biology to study how genes are regulated. This new knowledge impacted endocrinology and reproductive biology since it was largely known that the secretion of the internal glands affected the phenotypes, and expression of genes. Modern reproductive biology encompasses every level of biological study from genomics to ecology, encompassing cell biology, biochemistry, endocrinology and general physiology. All of these disciplines require a basic knowledge, both as a tool and as an essential aid to a fundamental understanding of the principles of life in health and disease. Overall, molecular biology is central to scientific studies in all living matter, impacting disciplines such as medicine, related health sciences, veterinary, agriculture and environmental sciences. In this book, the basic biochemistry of nucleic acids and proteins are reviewed. Methodologies used to study signaling and gene regulation in the endocrine/reproductive system are also discussed. Topics include mechanisms of hormone action and several endocrine disorders affecting the reproductive system. Professionals in the medical, veterinary and animal sciences fields will find exciting and stimulating material enhancing the breadth and quality of their research.
Molecular biology emerged from advances in biochemistry during the 1940s and 1950s, when the structure of the nucleic acids and proteins were elucidated. Beginning in the 1970s, with nucleic acid enzymology and the discovery of the restriction enzymes, the tools of molecular biology became widely available and applied in cell biology to study how genes are regulated. This new knowledge impacted endocrinology and reproductive biology since it was largely known that the secretion of the internal glands affected the phenotypes, and expression of genes. Modern reproductive biology encompasses every level of biological study from genomics to ecology, encompassing cell biology, biochemistry, endocrinology and general physiology. All of these disciplines require a basic knowledge, both as a tool and as an essential aid to a fundamental understanding of the principles of life in health and disease. Overall, molecular biology is central to scientific studies in all living matter, impacting disciplines such as medicine, related health sciences, veterinary, agriculture and environmental sciences. In this book, the basic biochemistry of nucleic acids and proteins are reviewed. Methodologies used to study signaling and gene regulation in the endocrine/reproductive system are also discussed. Topics include mechanisms of hormone action and several endocrine disorders affecting the reproductive system. Professionals in the medical, veterinary and animal sciences fields will find exciting and stimulating material enhancing the breadth and quality of their research.
Preface 6
Acknowledgments 7
Contents 8
Contributors 11
Part I The Basis for Molecular Reproductive Biology 13
1 Introduction to the Molecular Organization of the Endocrine/Reproductive System 14
1.1 Introduction 14
1.2 The Endocrine System: Classical and Current Concepts 14
1.2.1 Hormones and Hormone-Targets 15
1.2.2 Organization of the Extracellular Signaling Molecules 18
1.2.3 Sex-Specific Hormone Actions 18
1.2.4 Growth Factors and Cytokines 18
1.2.5 Dissolved Gases as Signaling Molecules 20
1.3 Regulation of Synthesis and Actions of the Signaling Molecules: The Concept of Feedback 20
1.4 Summary 21
2 Extracellular Signaling Receptors 23
2.1 Introduction 23
2.2 Cell Surface and Nuclear Receptors 23
2.2.1 Cell Surface Receptors 23
2.2.2 Nuclear Transcription Factor Receptors 25
2.3 Functional Properties of Receptors 25
2.4 Receptor Assays 26
2.4.1 Quantitative Analysis of Receptor mRNA 26
2.4.2 Immunoassays 26
2.4.3 Radioligand Binding Assays 27
2.4.4 Equilibrium Saturation-Binding Assay 28
2.5 Interpretation of the Equilibrium Saturation Binding Assay Data 28
2.6 Functional Receptor Assays 29
2.7 Regulation of Receptors 29
2.8 Receptor Terminology 30
2.9 Summary 31
3 The Molecules That Transmit Information into the Cell: The Intracellular Signaling Pathways 33
3.1 Introduction 33
3.2 Signaling Through Seven Transmembrane Receptors 33
3.2.1 G-Protein Molecular Switches 34
3.2.2 Signal Effectors and Second Messengers 35
3.3 Signaling Through Ion Channel Receptors 38
3.4 Signaling Through Enzyme-Linked Receptors 39
3.4.1 Tyrosine Kinase Receptors 40
3.4.2 Tyrosine Kinase Associated Receptors 42
3.4.3 Serine/Threonine Kinase Receptors 43
3.4.4 Guanylate Cyclase Associated Receptors 43
3.5 Regulation of Receptors and Signaling Pathways 44
3.6 Interactions Between Signaling Pathways 45
3.7 Summary 46
4 Introduction to Molecular Biology: Structure and Function of the Macromoleculesof Genetic Information 50
4.1 Introduction 50
4.2 Structure and Functions of the Nucleic Acids 50
4.2.1 DNA 51
4.2.2 RNA 53
4.3 Flow of Genetic Information: From DNA to RNA to Proteins 55
4.3.1 The Genetic Code and Protein Synthesis 55
4.4 Summary 57
5 Regulation of Gene Expression 59
5.1 Introduction 59
5.2 Transcriptional Regulation of Gene Expression: The Basic Transcription Unit 59
5.2.1 Promoters 59
5.2.2 Enhancers 60
5.2.3 Silencers 61
5.2.4 Boundary Elements 61
5.2.5 Response Elements 61
5.3 Transcription Factors 61
5.3.1 Coregulators 62
5.4 Transcription Factors Structural Motifs 62
5.4.1 Helix-Turn-Helix 62
5.4.2 Homeodomain Proteins 62
5.4.3 High Mobility Group Proteins 63
5.4.4 Zinc-Finger Transcription Factors 63
5.4.5 Leucine Zippers 65
5.4.6 Helix-Loop-Helix 65
5.5 Signaling Regulated Transcription 65
5.5.1 Changes in Chromatin Structure: CBP and CREB/CREM/ICER Family of Transcription Factors 65
5.5.2 Post-translational Modifications of Transcription Factors 66
5.5.3 Tissue-Specific Gene Expression 67
5.5.4 Epigenetic Regulation of Gene Expression 68
5.6 Regulation of Gene Expression by RNA Interference 69
5.7 Summary 69
6 Molecular Basis of Abnormal Phenotype 74
6.1 Introduction 74
6.2 Genetic Mutations 74
6.2.1 Gene Mutations 75
6.2.2 Chromosome Mutations 76
6.2.3 Genome Mutations 76
6.3 Summary 77
Part II The Tools of Molecular Reproductive Biology 79
7 Recombinant DNA Technology 80
7.1 Introduction 80
7.2 Restriction Enzymes 80
7.3 Recombination of DNA and Gene Libraries 81
7.4 Biological Systems Used in Molecular Biology 82
7.4.1 Microorganisms 82
7.4.2 Cloning Vectors 82
7.4.3 Tissues and Cells in Culture 85
7.4.4 Multicellular Organisms 85
7.5 Summary 86
8 Techniques for DNA Analysis 88
8.1 Introduction 88
8.2 Gel Electrophoresis 88
8.3 Southern Blot Analysis (Southern Blot Hybridization) 88
8.3.1 Methodology 88
8.4 DNA Sequencing 89
8.4.1 Sanger-Coulson Sequencing Methodology 89
8.5 DNA Fingerprinting and Profiling 89
8.6 Polymerase Chain Reaction 90
8.6.1 Methodology 90
8.7 Real-Time PCR 90
8.7.1 Real-Time PCR Using Double-Stranded DNA Dyes 91
8.7.2 Fluorescent Reporter Probe Method 91
8.8 Identification of Gene Mutations 91
8.8.1 Restriction Fragment Length Polymorphism (RFLP) 91
8.8.1.1 Methodology 91
8.8.2 Single-Stranded Conformational Polymorphism (SSCP) 93
8.8.2.1 Methodology 94
8.8.3 Denaturing Gradient Gel Electrophoresis (DGGE) 94
8.8.3.1 Methodology 94
8.8.4 Heteroduplex Analysis 94
8.8.4.1 Methodology 95
8.8.5 Chemical Mismatch Cleavage (CMC) or Enzyme Mismatch Cleavage (EMC) 95
8.8.5.1 Methodology 95
8.8.6 Protein Truncation Test (PTT) 95
8.8.6.1 Methodology 95
8.9 Techniques for Detection of Promoter Methylation 95
8.9.1 Bisulfite Treatment 96
8.9.2 Methylation Specific PCR (MSP) 96
8.9.3 Bisulfite Sequencing PCR (BSP) 96
8.10 Comparative Genomic Hybridization (CGH) 96
8.10.1 Methodology 96
8.11 Fluorescence In Situ Hybridization (FISH) 97
8.11.1 Methodology 97
8.12 Summary 98
9 Analyzing Gene Expression 102
9.1 Introduction 102
9.2 Measuring Steady-State Levels of mRNA 102
9.2.1 Northern Blot Analysis 104
9.2.2 Slot/Dot Plot Analysis 105
9.2.3 Solution Hybridization Assays 105
9.3 Primer Extension Analysis 105
9.4 Polymerase Chain Reaction Amplification of mRNA 106
9.5 In Situ Hybridization 107
9.6 Final Considerations 108
10 DNA Microarray Analysis 110
10.1 Introduction 110
10.2 Types of DNA Microarrays 110
10.2.1 By Purpose 110
10.2.2 By Method of Production 111
10.2.3 By the Number of Genes that can Be Analyzed 111
10.3 Microarray Related Resources 111
10.4 Personalized Medicine 112
10.5 The Use of DNA Microarrays in Reproductive Biology 112
10.5.1 Female Reproduction 112
10.5.2 Male Reproduction 113
10.5.3 Use of Microarrays for Discovery of New Biomarkers for Reproductive Traits 114
10.5.4 Reproductive Diseases 114
10.6 Future Directions 114
10.7 Summary and Concluding Remarks 115
10.8 Appendix of Public Databases for Microarray Data 115
11 Computer Assisted Analysis of Genes 118
11.1 Introduction 118
11.2 Data Retrieval Systems 118
11.2.1 Entrez 118
11.2.2 GenBank 118
11.2.3 Universal Protein Resource (UniProt) 119
11.2.4 The Ovarian Kaleidoscope Database 119
11.3 Computer-Based Molecular Analysis Tools 119
11.3.1 Sequence Formatting 120
11.3.2 Sequence Conversion 120
11.3.3 Analysis of Restriction Enzyme Recognition Sites 120
11.3.4 Design Oligonucleotide Primers 120
11.3.5 Sequence Alignment and Comparison 120
11.4 Summary 121
12 Introduction to Gene Therapy 123
12.1 Introduction 123
12.2 Methods for Gene Transfer 123
12.2.1 Non-Viral Vectors 123
12.2.2 Microinjection 123
12.2.3 Particle Bombardment 124
12.2.4 Electroporation 124
12.2.5 Synthetic Vectors 124
12.2.6 Viral Vectors 125
12.3 Tumor Gene Therapy Strategies 126
12.3.1 Mutation Compensation 127
12.3.2 Molecular Chemotherapy 127
12.3.3 Immunopotentiation 127
12.3.4 Alteration of Drug Resistance 127
12.4 Gene Therapy of Uterine Leiomyoma 127
Part III Molecular Regulation of Reproductive Hormones 133
13 GnRH-GnRH-Receptor System in the Mammalian Female Reproductive Tract 134
13.1 Introduction 134
13.2 Primary Structures of GnRH 134
13.3 Localization and Distribution Pattern of GnRH in the Female Reproductive System 135
13.4 Synthesis and Secretions of GnRH 135
13.5 GnRH Receptor 136
13.6 GnRH Signaling 137
13.7 Regulation of GnRH and GnRHR Gene Expressions in the Female Reproductive System 139
13.7.1 Regulation by Gonadal Steroids 140
13.7.2 Regulation by Gonadotropins 141
13.7.3 Regulation by Melatonin 141
13.7.4 Autocrine/Homologous Regulation of GnRH and GnRHR 142
13.8 Functional Roles of GnRH in Female Reproductive System 142
13.8.1 Antigonadotropic Effects of GnRH 142
13.8.2 Antiproliferative Effects of GnRH 142
13.8.3 Role of GnRH in Apoptosis 143
13.9 Summary 143
14 FSH: One Hormone with Multiple Forms, or a Family of Multiple Hormones 147
14.1 Introduction 147
14.2 Pituitary Gonadotrophs 147
14.3 Structure and Characteristics of FSH Genes 148
14.3.1 FSH -Subunit Gene 148
14.3.2 FSH -Subunit Gene 148
14.4 FSH Synthesis 149
14.4.1 Hormonal Control of FSH Gene Expression 149
14.4.2 Post-translational Processing 152
14.5 Isoforms of FSH 153
14.6 Three-Dimensional Structure of FSH Protein 156
14.7 Clinical Importance of FSH 157
14.8 Naturally Occurring Mutations within FSH 157
14.9 Summary 158
15 The FSH Receptor: One Receptor with Multiple Forms or a Family of Receptors 163
15.1 Introduction 163
15.2 Structure and Function of the FSHR 164
15.3 Expression of the FSH Receptor 164
15.4 Splice Variants of the FSHR 166
15.5 Post-translational Modification and Receptor Trafficking 169
15.6 Binding to FSH and Activation of the FSHR 170
15.7 FSHR Signaling Pathways 170
15.8 Naturally Occurring Mutations Within the FSHR 171
15.9 FSHR and Ovarian Cancer 174
15.10 Summary 174
16 Regulation of the Early Steps in Gonadal Steroidogenesis 177
16.1 Introduction 177
16.2 Transcriptional Control of Steroidogenesis 177
16.2.1 Hormonal Regulation of Gonadal StAR mRNA Expression 177
16.2.2 StAR Promoter Regulation in Gonadal Cells 178
16.2.3 Hormonal Regulation of Gonadal CYP11A1 mRNA Expression 181
16.2.4 CYP11A1 Promoter Regulation in Gonadal Cells 181
16.2.5 Hormonal Regulation of Gonadal HSD3B mRNA Expression 183
16.2.6 HSD3B Promoter Regulation in Gonadal Cells 183
16.3 Biochemistry and Post-translational Regulation 184
16.3.1 The Cholesterol Side-Chain Cleavage Complex (CSCC) 184
16.3.2 StAR 185
16.3.3 Congenital Lipoid Adrenal Hyperplasia (Lipoid CAH) 186
16.3.4 StAR-Independent Steroidogenesis 186
16.3.5 3-HSD 187
16.4 Summary and Conclusions 187
17 Prostaglandins and Their Mechanisms of Action in the Cyclic Ovary 196
17.1 Introduction 196
17.2 Biosynthesis of Prostaglandins 196
17.3 Prostaglandins Release from Cells and Subsequent Transport 197
17.4 Prostaglandin Receptors 198
17.5 Role of Prostaglandins in Ovulation 198
17.6 Role of Prostaglandins in Luteolysis 199
17.6.1 Luteal Endothelin System 200
17.6.2 Role of Endothelin in Mediating Luteolytic Actions of PGF 2 200
17.6.3 Luteolytic Capacity of Prostaglandins in the Young Corpus Luteum 201
17.7 Summary 202
18 Androgens-Molecular Basis and Related Disorders 206
18.1 Introduction 206
18.2 Androgen Biosynthesis and Metabolism in Males 206
18.3 Biological Effects of Androgens 208
18.3.1 Role of Androgens in Fetal Sexual Differentiation 208
18.3.2 Effects of Androgens at Puberty 208
18.4 Androgen Receptor 209
18.5 Androgen Receptor Gene Mutations 209
18.6 Androgen Disorders 210
18.6.1 Androgen Insensitivity Syndrome 210
18.6.1.1 Genetic Molecular Pathophysiology 210
18.6.1.2 Clinical Manifestations, Diagnosis, and Management 210
18.6.2 X-linked Spinal and Bulbar Muscular Atrophy 212
18.6.2.1 Genetic Molecular Pathophysiology 212
18.6.2.2 Clinical Manifestations, Diagnosis, and Management 212
18.6.3 5-reductase-2 Deficiency Syndrome 212
18.6.3.1 Genetic Molecular Pathophysiology 212
18.6.3.2 Clinical Manifestations, Diagnosis, and Management 213
18.7 Summary 213
19 Leptin as a Reproductive Hormone 216
19.1 Introduction 216
19.2 Leptin as a Neuroendocrine Regulator of Reproduction 216
19.3 Leptin as a Direct Regulator of Reproduction 218
19.3.1 Steroid Interactions 218
19.3.2 Puberty 219
19.3.3 Menstrual Cycle 219
19.3.4 Female Infertility 220
19.3.5 Pregnancy and the Maternal-Fetoplacental Unit 220
19.3.6 Male Reproduction 222
19.4 Summary 224
20 Neurosteroids and Sexual Behavior and Reproduction 229
20.1 Introduction 229
20.2 Neurosteroids 229
20.3 Receptor Types Targeted by Neurosteroids 229
20.4 Neurosteroids in Sexual Function 230
20.5 Neurosteroids in Sexual Behavior 231
20.5.1 Female Sexual Behavior 231
20.5.2 Male Sexual Behavior 232
20.6 Neurosteroids in Mood, Sexual Interest, and Gender-typycal Behaviors 232
20.6.1 Anxiety and Female Sexual Interest and Behavior 232
20.6.2 Anxiety and Male Sexual Interest and Behavior 233
20.7 The Future of Neurosteroids in the Clinic 233
20.8 Summary 234
Part IV Molecular Regulation of the Reproductive Organs and Tissues 238
21 Autocrine and Paracrine Regulation of the Ovary 239
21.1 Introduction 239
21.2 Selection of the Dominant Follicle 239
21.3 The Role of Steroids: The Two-Cell Two-Gonadotropin Concept 239
21.4 Intraovarian Regulators 240
21.4.1 Epidermal Growth Factor/Transforming Growth Factor- (EGF/TGF-) 240
21.4.2 Insulin-like Growth Factors 240
21.4.3 Transforming Growth Factor- ß 241
21.4.4 Fibroblastic Growth Factors 241
21.4.5 Neuronal Factors 242
21.4.6 Ovarian GnRH Peptides 242
21.4.7 Angiogenic Factor 242
21.5 Summary 244
22 Ovarian Endocrine Activity: Role of Follistatin, Activin, and Inhibin 247
22.1 Introduction 247
22.2 Biological Effects of Inhibin 248
22.3 Sources of Inhibin 248
22.4 Physiology of Immunoreactive Inhibin 248
22.4.1 Pubertal Development 248
22.4.2 Development of Specific and More Sensitive Methods for the Determination of Dimeric and Monomeric Inhibin 249
22.5 Inhibins as Reliable Markers of Ovarian Activity 249
22.5.1 Neonatal Period 249
22.5.2 Infancy and Childhood 250
22.5.3 Pubertal Development 250
22.5.4 Profile of Inhibin in the Normal Menstrual Cycle 250
22.6 Regulation of Inhibin Production by Granulosa Cells 251
22.7 Clinical Uses of Inhibin Assays 252
22.8 Summary 252
23 Hormonal and Molecular Regulation of the Cytochrome P450 Aromatase Gene Expressionin the Ovary 255
23.1 Introduction 255
23.2 Dynamics of P450 arom Gene Expressionin the Ovary 255
23.2.1 Expression of Aromatase in Ovarian Follicles 255
23.2.2 Aromatase Expression in Luteal Cells 257
23.3 Regulation of the Ovarian Aromatase Promoter 260
23.3.1 Structure of the Aromatase Gene 260
23.3.2 Regulation of the Cis-Elements in the Aromatase Gene Ovarian Promoter 261
23.4 Summary 262
24 Epigenetic Mechanisms of Ovarian Gene Regulation 268
24.1 Introduction 268
24.2 Histone Modifications 268
24.2.1 Acetylation and Deacetylation 268
24.2.2 Methylation and Demethylation 269
24.2.3 Phosphorylation 270
24.2.4 Ubiquitination, ADP-Ribosylation, and Sumoylation 270
24.2.5 Bromo and Chromo Domain Proteins 270
24.3 Detection of Histone Modifications 270
24.3.1 Chromatin Immunoprecipitation Assay 270
24.3.2 DNA Methylation 271
24.4 The Dynamic Ovarian Follicle and the Study of Histone Modifications 272
24.5 Summary 273
25 Ovarian Function and Failure: The Role of the Oocyte and Its Molecules 277
25.1 Introduction 277
25.2 Oocyte Quality and Its Role in Fertility 277
25.3 In Search of Other Markers of Oocyte Quality 278
25.4 Aging: Mitochondria, DNA Check Point, and Lipids 279
25.5 Summary 283
26 Molecular Control of Corpus Luteum Function 287
26.1 Introduction 287
26.2 Luteinization 287
26.2.1 Intracellular and Genomic Effects of the LH surge 287
26.2.2 Granulosa Cell Exit from the Proliferative Cycle 289
26.2.3 Role of the Oocyte in Luteinization 290
26.2.4 Structural Changes 290
26.3 Luteal Steroidogenesis 292
26.4 Hormonal Regulation 294
26.4.1 Role of Luteinizing Hormone 294
26.4.2 Role of Prolactin (PRL) 295
26.4.3 Role of Estradiol 296
26.4.4 Role of Progesterone 296
26.5 Luteolysis 297
26.5.1 Factors Involved in Functional Regression 297
26.5.2 Structural Regression 299
26.6 Rescue of the Corpus Luteum 300
27 The Molecular Landscape of Spermatogonial Stem Cell Renewal, Meiotic Sex Chromosome Inactivation, and Spermatic Head Shaping 309
27.1 Introduction 309
27.2 General Organization and Dynamics of the Seminiferous Epithelium 309
27.3 Extrinsic and Intrinsic Bioregulation of the Spermatogonial Cell Progeny 310
27.4 Molecular Aspects Chromosome Transcription and Inactivation During Meiotic Prophase 312
27.5 Molecular Aspects of Spermatid Head Shaping 314
27.6 Concluding Remarks 316
Appendix A Glossary of Molecular Term 318
Appendix B Glossary of Terms and Acronyms 327
Index 341
| Erscheint lt. Verlag | 13.6.2009 |
|---|---|
| Zusatzinfo | XVI, 361 p. |
| Verlagsort | New York |
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Medizinische Fachgebiete ► Gynäkologie / Geburtshilfe |
| Medizinische Fachgebiete ► Innere Medizin ► Endokrinologie | |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
| Technik | |
| Schlagworte | endocrinology • genomics • Intracellular signaling • Molecular Biology • Reproduction • signaling pathways |
| ISBN-10 | 0-387-88186-7 / 0387881867 |
| ISBN-13 | 978-0-387-88186-7 / 9780387881867 |
| Haben Sie eine Frage zum Produkt? |
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