Human Chorionic Gonadotropin (hCG) (eBook)

Front Cover 1
Human Chorionic Gonadotropin (hCG) 4
Copyright Page 5
Table of Contents 6
Foreword 12
About the Author 16
Abbreviations 18
Contributors 22
Part A: Introduction 24
Chapter 1 The Expanding World of hCG 26
Chapter 2 History and Introduction to Human Chorionic Gonadotropin (hCG): One Name for at Least Three Independent Molecules 36
Chapter 3 Introduction to Pregnancy Implantation, Villous Formation, and Hemochorial Placentation 46
Part B: Genetics, Synthesis, Secretion, Structure, and Degradation of hCG 58
Chapter 4 The Molecular Genetics of hCG 60
4.1 The LH/hCG Gene Cluster 60
4.2 Control of hCG Gene Expression: hCG& #945
4.3 Control of hCG Gene Expression: hCG& #946
Chapter 5 Structure, Synthesis, Secretion, and Function of hCG 72
5.1 Amino Acid Sequence of hCG 73
5.2 Carbohydrate Structure of hCG 73
5.3 hCG Primary Structure 75
5.4 hCG Secondary Structure 77
5.5 hCG Tertiary Structure 77
5.6 hCG Quaternary Structure 78
5.7 Combination of hCG Subunits 80
5.8 Synthesis and Secretion of hCG 80
5.9 Functions of hCG 82
Chapter 6 Comparison of the Structures of hCG and Hyperglycosylated hCG 90
6.1 Peptide Structure of hCG-H 90
6.2 N- and O-Linked Oligosaccharide Structures of hCG-H 95
Chapter 7 Structures of Free & #945
7.1 Free & #945
7.2 Free & #946
Chapter 8 Glycobiology of hCG 110
8.1 Characteristic Features of the Sugar Chains of Glycoproteins 110
8.2 Biosynthetic Pathways of the Sugar Chains of Glycoproteins to Form Their Characteristic Features 111
8.3 The hCG Sugar Chains from Urine of Pregnant Women and Placenta 113
8.4 Characteristic Features of the Sugar Chains of Free & #945
8.5 Comparative Studies of the N-Linked Sugar Chains of hCG Samples Purified from the Urine of Patients with Various Trophoblastic Diseases 119
8.6 Alteration Induced in the O-Linked Sugar Chains of hCG by Malignant Transformation of Trophoblasts 121
8.7 Altered Expression of GnT-IV in Choriocarcinoma Cells 122
8.8 Glycosylated hCG as a Diagnostic Marker of Trophoblastic Diseases 123
8.9 Functional Role of the hCG Sialic Acid Residues 125
8.10 Future Prospects 127
Chapter 9 Degradation Products of hCG, Hyperglycosylated hCG, and Free & #946
9.1 Pure hCG Preparations 137
9.2 Nicking and Enzyme Cleavage 139
9.3 Dissociation 140
9.4 Liver Clearance 140
9.5 Degradation with Pregnancy Advancement 141
Chapter 10 Three-Dimensional Structure of hCG 146
10.1 hCG 147
10.2 Hyperglycosylated hCG 149
10.3 Free & #946
Part C: Biological Function of hCG 152
Chapter 11 Paradigm Shift on the Targets of hCG Actions 154
11.1 Summary and Perspectives 158
Chapter 12 The hCG Receptor 162
Chapter 13 Biological Function of Hyperglycosylated hCG 168
Chapter 14 Biological Function of the Free & #946
14.1 hCG& #946
14.2 hCG& #946
14.3 The Biological Action of hCG& #946
14.4 hCG Cancer Vaccines 184
Part D: Clinical Applications 196
Chapter 15 Use of hCG in Reproductive Dysfunction 198
15.1 Historical Overview and Perspective 199
15.2 Considerations of hCG Administration within Clinical Protocols 202
15.3 Timing Administration of hCG—Ultrasound Monitoring, Progesterone Patterns, and Endogenous LH Surge Patterns 206
15.4 Risks of Ovulation Management with hCG 207
15.5 Efficacy of LUF Syndrome 209
15.6 Considerations of hCG Administration for Timing IUI 211
15.7 High-Order Multiple Pregnancies 215
Chapter 16 hCG in Assisted Reproduction 224
16.1 The Ovarian Cycle and hCG Use in Assisted Reproduction 225
16.2 The Follicular Phase: The Role of LH 225
16.3 The Periovulatory Phase and the Mid-Cycle LH Surge 226
16.4 The Follicular–Luteal Transition 227
16.5 The Luteal–Placental Shift 228
16.6 The Potential Role of hCG in Implantation 228
16.7 hCG in the Management of Normal Pregnancy 230
16.8 Hyperstimulation Syndrome 231
16.9 hCG in the Management of Ectopic Pregnancy 232
16.10 Conclusions 233
Chapter 17 Illicit Use of hCG in Dietary Programs and Use to Promote Anabolism 236
17.1 Dietary Programs 236
17.2 hCG and Anabolism Promotion 237
Part E: hCG Tests 242
Chapter 18 Antibodies for Intact hCG, for Total hCG, for Free Subunits, Glycosylation Variants, and for hCG Fragments 244
18.1 Intact hCG and Total hCG Assay 244
18.2 Free Subunit, Glycosylation Variant, and Fragment Assay 247
18.3 Generating an Immunoassay 248
Chapter 19 Quantitative hCG Assays 250
19.1 Manual Immunometric Assays 250
19.2 Automated Immunometric Assays 252
19.3 Competitive Radioimmunoassays 254
Chapter 20 False Positive hCG Assays 256
20.1 False Positive hCG Test 256
Chapter 21 Specificity of Different hCG Assays 264
21.1 Clinical Laboratory Tests 265
21.2 Point-of-Care Tests 270
21.3 Over-the-Counter Tests 271
Chapter 22 Point-of-Care Pregnancy Tests 274
22.1 Point-of-Care Tests 275
Chapter 23 Over-the-Counter Pregnancy Tests 278
23.1 How OTC Tests Work 278
23.2 Accuracy of OTC Tests 279
Chapter 24 hCG Standards 286
24.1 First IS 287
24.2 Second IS 287
24.3 Third IS 287
24.4 IRR for hCG and Related Substances 288
24.5 Future Prospects 291
24.6 Recombinant hCG 292
Part F: Test Applications 296
Chapter 25 Background hCG 298
25.1 Serum hCG 299
25.2 Urine hCG 300
25.3 The Cancer Predicament 304
25.4 The Menopausal hCG Quandary 304
Chapter 26 Pregnancy Testing 308
Chapter 27 Predicting Spontaneously Aborted (SAB) Pregnancies 314
27.1 Pregnancy Outcome Markers 315
27.2 Early Pregnancy hCG 316
27.3 Testing for hCG-H 317
Chapter 28 hCG, Hyperglycosylated hCG, and Free & #946
28.1 Down Syndrome Screening 322
28.2 Preeclampsia Screening 324
Chapter 29 hCG in Monitoring Gestational Trophoblastic Diseases 328
Chapter 30 Use of Hyperglycosylated hCG as a Unique Marker of Gestational Trophoblastic Neoplasms 334
30.1 Quiescent Gestational Trophoblastic Disease 335
30.2 Minimally Aggressive Gestational Trophoblastic Neoplasm 337
30.3 Gestational Trophoblastic Neoplasm Classification 350
Chapter 31 Pituitary hCG and Familial hCG 352
31.1 Structure of Pituitary hCG 353
31.2 Biological Function of Pituitary hCG 353
31.3 Occurrence of Pituitary hCG 355
31.4 Familial hCG Syndrome 359
Chapter 32 hCG, Free & #946
32.1 hCG and Tumor Markers 366
Part G: Basic Methods 372
Chapter 33 hCG and Hyperglycosylated hCG Purification and Analysis from Serum, Urine, and Culture Fluids 374
33.1 Urine hCG and hCG-H 374
33.2 Culture Fluid hCG and hCG-H 375
33.3 Serum hCG and hCG-H 376
33.4 Analysis 376
Chapter 34 Dissociation, Desialylation, and Cleavage of hCG 378
34.1 Dissociation 378
34.2 Desialylation 378
34.3 Cleavage of & #946
34.4 Reduction and S-Carboxymethylation of hCG 379
34.5 Tryptic Digest of Reduced and S-Carboxymethylated hCG Subunit 379
Chapter 35 hCG and Free & #946
Part H: Evolution, Summary, and the Future 384
Chapter 36 Evolution of hCG, Evolution of Humans, and Evolution of Human Pregnancy Disorders and Cancer 386
36.1 CG Evolution 387
36.2 CG, CG-H, and the Evolution of Humans 389
36.3 CG Evolution and the Development of Pregnancy Disorders 394
36.4 hCG and Cancer 395
36.5 Personal Thoughts 397
Chapter 37 Summary: hCG a Remarkable Molecule 400
37.1 hCG Extremities 400
37.2 Structure of hCG 400
37.3 Biological Functions 400
37.4 Detection of hCG& #946
37.5 Administration of hCG 401
37.6 Detection of hCG Outside Pregnancy 402
37.7 Synthesis and Degradation of hCG 402
Chapter 38 hCG and the Future 404