Endocrine Disruptors: Effects on Male and Female Reproductive Systems

ENDOCRINE DISRUPTORS: Effects on Male and Female Reproductive Systems, Second Edition......Page 2
Dedication......Page 4
Preface......Page 5
Editor......Page 8
Contributors......Page 9
Acknowledgments......Page 12
Table of Contents......Page 13
Section I: Effect on the Female Reproductive System......Page 15
CONTENTS......Page 16
1.1 INTRODUCTION......Page 17
1.2 NONGENOMIC ACTIONS OF STEROIDS......Page 19
1.2.2 ENDOCRINE DISRUPTION OF NONGENOMIC STEROID ACTIONS......Page 20
1.2.3.1 Role of Oocyte Progestin Membrane Receptors......Page 21
1.2.3.2 Characteristics of Ovarian MIS Membrane Receptors in Fishes......Page 22
1.2.3.3 Xenoestrogen Binding to the Ovarian MIS Membrane Receptor in Fish......Page 23
1.2.3.4 Xenoestrogen Interference with MIS Induction of Oocyte Maturation......Page 25
1.2.3.5 Significance of Receptor Location in Plasma Membrane......Page 27
1.2.4.2 Characteristics of Sperm MIS Membrane Receptor in Fishes......Page 28
1.2.4.3 Role of Sperm MIS Membrane Receptor in Sperm Motility......Page 30
1.2.4.4 Xenoestrogen Binding to Sperm MIS Membrane Receptor......Page 31
1.2.4.5 Effects of Xenobiotics on Sperm Motility......Page 32
1.2.4.6 Current Issues in Endocrine Disruption of Nongenomic Steroid Actions......Page 33
1.2.5 CLONING, IDENTIFICATION, AND CHARACTERIZATION OF PROGESTIN MEMBRANE RECEPTORS IN FISH AND OTHER VERTEBRATES......Page 34
1.3.1 STIMULATORY 5-HT-GNRH NEUROENDOCRINE PATHWAY CONTROLLING LH SECRETION IN FISH......Page 37
1.3.2.1 Effects of Aroclor 1254 on Hypothalamic Tryptophan Hydroxylase and Monoamine Oxidase Activities......Page 39
1.3.2.3 Effects of PCB, PCPA, and PCB+5-HTP on GnRH Content in the POAH and Pituitary......Page 40
1.3.2.4 Effects of PCB, PCPA, and PCB+5-HTP on Basal and 5-HT-Induced GnRH Release from the POAH and Pituitary Slices Incubated In Vitro......Page 41
1.3.2.5 Effects of PCB, PCPA, and PCB+5-HTP on Basal and GnRHa-Induced LH Secretion......Page 42
1.3.2.6 Effects of PCB and GnRH Replacement Therapy on GnRH Receptors and LH Secretion......Page 43
1.3.3 EFFECT OF LEAD ON HYPOTHALAMIC MONOAMINERGIC SYSTEMS AND NEUROENDOCRINE FUNCTION......Page 45
REFERENCES......Page 48
CONTENTS......Page 59
2.1 INTRODUCTION......Page 60
2.2 DEVELOPMENTAL BASIS OF ADULT DISEASE......Page 61
2.3 DES AS A PROTOTYPE ENVIRONMENTAL ESTROGEN......Page 62
2.4.1 EARLY REPRODUCTIVE SENESCENCE AND DYSFUNCTION......Page 64
2.4.3 OVIDUCTAL TOXICITY......Page 65
2.4.4 UTERINE FIBROIDS AND ADENOCARCINOMA  AND VAGINAL TOXICITY......Page 67
2.5 LOW-DOSE EFFECTS......Page 69
2.6 MECHANISMS OF REPRODUCTIVE TOXICITY......Page 72
2.7 SUMMARY AND CONCLUSION......Page 73
REFERENCES......Page 74
CONTENTS......Page 78
3.1 INTRODUCTION......Page 79
3.2.1.1 Prenatal Development......Page 80
3.2.1.2.4 Antral Follicles......Page 81
3.2.2.1 Apoptosis as Atresia......Page 82
3.3 IMPACT OF XENOBIOTIC-INDUCED DAMAGE ON OVARIAN FUNCTION......Page 83
3.4.1.2 Chemotherapeutic Agents......Page 86
3.4.1.3 Cigarette Smoking......Page 87
3.4.1.4 Polycyclic Aromatic Hydrocarbons......Page 88
3.4.1.5 Occupational Chemicals......Page 89
3.4.1.6 Other Ovotoxic Agents......Page 90
3.4.2.2 Polycyclic Aromatic Hydrocarbons......Page 92
3.4.2.4 Halogenated Aryl Hydrocarbons......Page 93
3.4.1.5 Occupational Chemicals......Page 94
3.5.2 DETOXIFICATION......Page 95
3.5.3.2 Polycyclic Aromatic Hydrocarbons......Page 96
3.5.3.3 4-Vinylcyclohexene......Page 97
3.6.1 CELL DEATH......Page 98
3.6.2 SITES OF CELLULAR DAMAGE......Page 100
REFERENCES......Page 102
CONTENTS......Page 112
4.1 INTRODUCTION: P, P’ ? DDE 1,1-DICHLORO-2,2-BISP-CHLOROPHENYLETHYLENE AND HCBHEXACHLOROBENZENE......Page 113
4.1.2 DESCRIPTION OF HCB......Page 114
4.2 DDE: OVERVIEW OF TOXIC MECHANISMS AND EFFECTS......Page 115
4.2.1 EFFECTS OF DDE ON FETAL AND EMBRYONIC MAMMALIAN CELLS AT LOW ENVIRONMENTAL CONCENTRATIONS......Page 118
4.2.2 SHORT-TERM EFFECTS OF DDE TOXICITY ON IMMATURE MAMMALIAN CELLS......Page 119
4.2.3 LONG-TERM EFFECTS OF DDE TOXICITY ON IMMATURE MAMMALIAN CELLS......Page 123
4.3 HCB: OVERVIEW OF TOXIC MECHANISMS AND EFFECTS......Page 124
4.3.2 SHORT-TERM EFFECTS OF HCB TOXICITY ON IMMATURE MAMMALIAN CELLS......Page 128
4.3.3 LONG-TERM EFFECTS OF HCB TOXICITY ON IMMATURE MAMMALIAN CELLS......Page 133
4.4 EFFECTS OF HCB+DDE MIXTURES ON FETAL AND EMBRYONIC MAMMALIAN CELLS AT LOW ENVIRONMENTAL CCONCENTRATIONS......Page 134
4.4.2 LONG-TERM EFFECTS OF HCB+DDE MIXTURE TOXICITY ON IMMATURE MAMMALIAN CELLS......Page 135
REFERENCES......Page 139
5.1 INTRODUCTION......Page 145
5.2.1 LIGNANS......Page 147
5.2.2 ISOFLAVONOIDS......Page 148
5.2.3 METABOLISM......Page 149
5.4.1 ESTROGEN RECEPTOR BINDING......Page 152
5.4.2 MECHANISMS OF ACTION NOT MEDIATED BY ESTROGEN RECEPTORS......Page 154
5.5 PHYSIOLOGICAL EFFECTS......Page 155
5.5.1 HORMONAL AND REPRODUCTIVE EFFECTS......Page 156
5.5.2 DEVELOPMENTAL EFFECTS......Page 158
5.5.2.1 Phytoestrogen Exposure in Infants......Page 159
5.5.3 MENOPAUSAL SYMPTOMS......Page 161
5.6 OSTEOPOROSIS......Page 162
5.7 THE CANCER CONNECTION......Page 163
5.7.1 BREAST CANCER......Page 164
5.7.2 HUMAN DATA......Page 165
5.8 CHOLESTEROL AND HEART DISEASE......Page 166
5.10 CONCLUSION......Page 168
REFERENCES......Page 169
CONTENTS......Page 184
6.1 INTRODUCTION......Page 185
6.2.1 CUMULATIVE EFFECT OF XENOESTROGENS......Page 186
6.2.2 NOVEL XENOESTROGENS......Page 187
6.2.3 DEVELOPMENTAL EFFECTS......Page 188
6.3 NEOPLASIA......Page 189
6.4.1 GENETIC ORIGIN AND THE SOMATIC MUTATION THEORY OF CARCINOGENESIS......Page 190
6.4.3 CONTROL OF CELL PROLIFERATION AND NEOPLASIA......Page 191
6.4.3.2 Control of Initiation of Cell Proliferation by Estrogens Step 1......Page 192
6.4.3.3 Control of the Expression of the Proliferative Shutoff by Estrogens Step-2 in Normalcy, Carcinogenesis, and Tumor Regression......Page 194
6.4.4 EPIGENETIC ORIGIN: TISSUE MAINTENANCE AND NEOPLASIA......Page 195
6.5.1 HORMONES AS MUTAGENS......Page 196
6.5.2 HORMONES AS PROMOTERS......Page 197
6.5.3 HORMONES AS TERATOGENS ACCORDING TO THE TOFT......Page 198
6.5.3.1 The DES Model......Page 199
6.5.4 HORMONES AS AGENTS OF TISSUE MAINTENANCE AND REMODELING......Page 200
6.6.3 OVARIAN HORMONES AND NEOPLASIA......Page 201
6.6.3.2 Mammary Gland Tumors......Page 202
6.6.3.4 Testicular Neoplasias......Page 204
6.6.3.5 Prostate Cancer......Page 205
6.7.2 NEOPLASIAS IN ANIMALS TREATED WITH ESTROGENIC PESTICIDES......Page 206
6.8 PESTICIDES AND BREAST CANCER......Page 207
6.9 DISCUSSION AND CONCLUSIONS......Page 209
REFERENCES......Page 211
7.1 INTRODUCTION......Page 225
7.2.1 TRANSCRIPTIONAL ACTIVATION BY ESTROGEN RECEPTOR......Page 229
7.2.3 EPIGENETIC EFFECTS......Page 235
7.3 INTRACELLULAR SIGNALING MECHANISMS......Page 236
7.4.1 ESTROGEN SYNTHESIS......Page 238
7.4.2.1 Catechol Estrogens and Reactive Metabolites......Page 240
7.4.2.2 CYP450 and the Aryl Hydrocarbon Receptor Pathway......Page 241
7.4.2.3 PXR and CAR Regulated CYP450......Page 242
7.4.2.4 Conjugating Enzymes......Page 243
REFERENCES......Page 244
CONTENTS......Page 256
8.1.1 INTRODUCTION......Page 257
8.1.2 TCDD AND RELATED COMPOUNDS: BIOCHEMICAL AND TOXIC RESPONSES......Page 258
8.1.3 IDENTIFICATION OF THE ARYL HYDROCARBON RECEPTOR AHR......Page 259
8.1.4 MOLECULAR MECHANISMS OF AHR-MEDIATED TRANSACTIVATION......Page 261
8.1.5 MODULATION OF AH-RESPONSIVENESS BY THE ER IN HUMAN BREAST CANCER CELL LINES......Page 263
8.2.2.1 Inhibition of Mammary Tumor Growth by TCDD......Page 265
8.2.2.2 Antiestrogenic Activity of TCDD and Related Compounds in Laboratory Animals......Page 266
8.2.2.3.1 MCF-7 and T47D Cells......Page 267
8.2.2.3.3 Inhibition of ER-Negative Breast Cancer Cell Growth by TCDD......Page 268
8.2.2.3.4 Inhibition of E2-Induced Cell Cycle Enzymes by TCDD......Page 270
8.2.2.4.1 Role of the AhR......Page 271
8.2.2.4.3 Inhibitory DREs iDREs as Genomic Targets for the AhR......Page 272
8.2.2.4.5 Other Mechanisms of Inhibitory AhR-ER alpha Crosstalk......Page 273
8.2.3.1 Introduction......Page 274
8.2.3.2 Alternate-Substituted PCDFs......Page 275
8.2.3.3 Substituted DIMs......Page 276
REFERENCES......Page 282
Section II: Effect on the Male Reproductive System......Page 295
CONTENTS......Page 296
9.1 INTRODUCTION......Page 297
9.2 BACKGROUND......Page 298
9.3.2 SERTOLI CELLS......Page 299
9.5.1 ENVIRONMENTAL AGENTS......Page 300
9.5.1.2 Heavy Metals......Page 302
9.5.2.3 Chemotherapeutic Agents......Page 303
9.6 MECHANISMS OF ACTION OF ENDOCRINE DISRUPTORS......Page 304
9.6.4 ALTERED HORMONE RECEPTOR RECOGNITION/BINDING......Page 305
9.6.5 ALTERED HORMONE POST-RECEPTOR ACTIVATION......Page 306
9.7 ASSESSMENT OF TOXICITY......Page 307
9.7.1 IN VITRO SYSTEMS......Page 308
9.7.2 IN VIVO SYSTEMS......Page 309
9.7.3 SPERM NUCLEAR INTEGRITY ASSESSMENT......Page 310
9.9 SUMMARY......Page 311
REFERENCES......Page 312
CONTENTS......Page 318
ABSTRACT......Page 319
10.1 INTRODUCTION......Page 320
10.1.1 IN VITRO AND IN VIVO ANDROGENIC EFFECTS OF PULP AND PAPER MILL EFFLUENTS IN THE LABORATORY AND THE FIELD: ENVIRONMENTAL ANDROGENS REVEALED......Page 321
10.2 IN VITRO AND IN VIVO STUDIES WITH FEEDLOT EFFLUENTS AND TRENBOLONE, AN ANABOLIC STEROID PRESENT IN SOME CATTLE FEEDLOT EFFLUENTS......Page 324
10.3.1 THE FUNGICIDE VINCLOZOLIN ? IN VITRO AND SHORT-TERM IN VIVO EFFECTS OF AN AR ANTAGONIST......Page 326
10.3.2 DOSE-RESPONSE DEVELOPMENTAL EFFECTS OF VINCLOZOLIN......Page 328
10.3.3 PUBERTAL EFFECTS OF VINCLOZOLIN......Page 329
10.3.4 PROCYMIDONE ? IN VITRO AND SHORT-TERM IN VIVO EFFECTS......Page 330
10.3.5 DOSE-RESPONSE DEVELOPMENTAL EFFECTS OF PROCYMIDONE IN THE MALE RAT......Page 331
10.4.2 DEVELOPMENTAL EFFECTS OF LINURON IN THE MALE RAT......Page 332
10.5.1 IN VITRO EFFECTS AND SHORT-TERM IN VIVO EFFECTS OF P,P’ DDE......Page 333
10.6.1 IN VITRO EFFECTS OF THE PROCHLORAZ, A CONAZOLE FUNGICIDE......Page 334
10.7.1 “ANTIANDROGENIC? EFFECTS OF PHTHALATE ESTERS DURING DEVELOPMENT......Page 335
10.8.1 ANTIANDROGENIC EFFECTS OF PBDE-71......Page 338
10.9.1 MIXTURES OF “ANTIANDROGENS?: AR ANTAGONISTS VERSUS INHIBITORS OF STEROIDOGENESIS......Page 340
REFERENCES......Page 341
CONTENTS......Page 349
11.1 INTRODUCTION......Page 350
11.3.1 TESTOSTERONE AND DEVELOPMENT OF MALE REPRODUCTIVE SYSTEM......Page 351
11.3.2 TESTOSTERONE AS THE SEX HORMONE ? ROLE IN ERECTILE FUNCTION......Page 353
11.4.1.1 Antiandrogens......Page 355
11.4.1.3 Aryl Hydrocarbon Ah Receptor Agonists......Page 356
11.5 HOW ENVIRONMENTAL ESTROGENS DIFFER FROM NATURAL HORMONES......Page 357
11.6.1 ROLE OF HYPOGONADISM......Page 358
11.6.2 CONTROVERSIES RELATED TO HYPOGONADISM AND ED......Page 359
11.7.1 PRIMARY HYPOGONADISM......Page 362
11.8.1 NEUROLOGICAL CAUSES OF MALE SEXUAL DYSFUNCTION......Page 363
11.8.4 RENAL DISEASE......Page 364
11.8.6 HYPERPROLACTINEMIA......Page 365
11.9 ENDOCRINE DISRUPTORS AND ED......Page 366
11.9.1.2 Pesticides......Page 368
11.9.2.2 Depression and Related Drugs......Page 369
11.9.3.3 Alcohol......Page 370
11.9.4.2 Other Phytoproducts......Page 371
11.9.5 ENVIRONMENT AND ED......Page 372
11.10 CONCLUSION......Page 373
REFERENCES......Page 374
CONTENTS......Page 382
12.1 INTRODUCTION......Page 383
12.2 HISTORICAL OVERVIEW OF THE PROSTATE......Page 384
12.3.1 PROSTATE DEVELOPMENT......Page 385
12.3.2 EVIDENCE FOR HOMOLOGY OF THE RODENT DORSOLATERAL AND HUMAN PROSTATE......Page 387
12.4.1 TESTOSTERONE AND 5alpha-DIHYDROTESTOSTERONE DHT......Page 390
12.4.2 GROWTH FACTOR SIGNALING BETWEEN MESENCHYME AND EPITHELIUM......Page 391
12.5.1 INHIBITORY EFFECTS OF HIGH, PHARMACOLOGICAL DOSES OF ESTROGEN......Page 393
12.5.2 STIMULATORY EFFECTS OF LOW, PHYSIOLOGICAL DOSES OF ESTROGEN......Page 395
12.5.3 MECHANISMS OF EFFECTS OF LOW DOSES OF ESTROGEN......Page 396
12.6 ENVIRONMENTAL ENDOCRINE-DISRUPTING ESTROGENIC CHEMICALS ALTER PROSTATE DEVELOPMENT......Page 399
12.7 ESTROGEN AND ADULT PROSTATE PATHOLOGY......Page 404
12.8 SUMMARY......Page 405
REFERENCES......Page 406
13.1 ABSTRACT......Page 414
13.2 INTRODUCTION......Page 415
13.3.2 PROSTATIC ZINC CONTENT AND PROSTATE CARCINOGENESIS......Page 416
13.3.3 DIETARY ZINC AND PROSTATE CANCER RISK......Page 417
13.4.2 CD IS A SUSPECTED CARCINOGEN FOR THE HUMAN PROSTATE......Page 418
13.4.3 CADMIUM IS A PROVEN CARCINOGEN FOR THE RAT PROSTATE......Page 419
13.4.4 MECHANISMS OF CADMIUM-INDUCED CARCINOGENESIS......Page 420
13.4.6 INTERPLAY BETWEEN CADMIUM AND OTHER HEAVY METALS IN PROSTATE CARCINOGENESIS......Page 421
13.4.7 METALLOTHIONEINS AND CADMIUM-INDUCED CARCINOGENICITY......Page 422
13.5 COPPER, NICKEL, AND ARSENIC......Page 423
REFERENCES......Page 424