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Human Chorionic Gonadotropin (hCG)

Laurence A. Cole

 

Verlag Elsevier Reference Monographs, 2010

ISBN 9780123849083 , 405 Seiten

Format PDF, ePUB, OL

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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: hCGα

61

4.3 Control of hCG Gene Expression: hCGβ

64

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 α- and β-Subunits

102

7.1 Free α-Subunit

102

7.2 Free β-Subunit

105

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 α-Subunit

117

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 β-Subunit

136

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 β-Subunit

149

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 β-Subunit: Expression and Treatment Target in Cancer

176

14.1 hCGβ Gene Expression in Cancer

178

14.2 hCGβ Expression in Epithelial Cancer

178

14.3 The Biological Action of hCGβ on Epithelial Tumors

181

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 β-Subunit in Predicting Down Syndrome Pregnancies and Preeclampsia

322

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 β-Subunit, and β-Core Fragment as Markers of Malignancies

366

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 β-Subunit C-Terminal Peptide

379

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 β-Subunit Producing Cell Lines

380

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 hCGβ Polypeptide Group of Molecules

401

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