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  • Produktbild: Estrogens and Antiestrogens I
  • Produktbild: Estrogens and Antiestrogens I

Estrogens and Antiestrogens I Physiology and Mechanism of Action of Estrogens and Antiestrogens

Aus der Reihe Handbook of Experimental Pharmacology

Fr. 765.00

inkl. gesetzl. MwSt., Versandkostenfrei

Beschreibung

Produktdetails

Einband

Gebundene Ausgabe

Erscheinungsdatum

30.07.1999

Herausgeber

Michael Oettel + weitere

Verlag

Springer Berlin

Seitenzahl

409

Maße (L/B/H)

23.5/15.5/3.2 cm

Gewicht

896 g

Auflage

1999

Sprache

Englisch

ISBN

978-3-540-65016-4

Beschreibung

Produktdetails

Einband

Gebundene Ausgabe

Erscheinungsdatum

30.07.1999

Herausgeber

Verlag

Springer Berlin

Seitenzahl

409

Maße (L/B/H)

23.5/15.5/3.2 cm

Gewicht

896 g

Auflage

1999

Sprache

Englisch

ISBN

978-3-540-65016-4

Herstelleradresse

Springer-Verlag GmbH
Tiergartenstr. 17
69121 Heidelberg
DE

Email: ProductSafety@springernature.com

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  • Produktbild: Estrogens and Antiestrogens I
  • Produktbild: Estrogens and Antiestrogens I
  • History of Estrogen Research.- 1 History of Estrogen Research.- A. The Classical Experiments of Extirpation and Reimplantation.- I. Ovarian Extracts.- B. Isolation of Estrogens.- C. Analysis of the Steroid Structure; Nomenclature and Standardization.- D. Partial and Total Synthesis of Estrogens.- E. Localization of the Estrogen Production.- F. Estrogens in Body Fluids and Tissues.- G. Estrogens in Food.- H. Estrogen Determination.- I. Estradiol Effects at the Target Organs.- I. Vagina and Endometrium.- II Breasts.- III. Hypothalamus and Pituitary.- J. Biogenesis and Metabolism of Estrogens.- K. Physiological Effects of Estrogens.- I. Genomic Actions.- II. Non-genomic Actions.- L. Mechanism of Action of Estrogens.- M. Effects on Lipids.- N. Effects on Coagulation.- O. Estrogens in Pregnancy.- P. Fetal Endocrinology.- Q. Estrogens for Treatment.- I. Preparations.- II. Treatment of Cycle Anomalies, Bleeding Disturbances and Dysmenorrhea.- R. Side Effects of Estrogens.- S. Treatment in Pregnancy.- T Treatment of Climacteric Complaints.- U. Estrogens and Carcinogenesis.- V. Estrogens and Life Expectancy.- References.- 1: Chemistry of Estrogens and Antiestrogens.- 2 Steroidal Estrogens.- A. Introduction.- B. Total Synthesis.- C. Partial Synthesis.- I. Ring-A Substitution.- II. Ring-B Substitution..- III. Ring-C Substitution.- IV. Ring-D Substitution.- V. The Periphery.- D. Labeling of Estradiol and its Derivatives.- E. Bioconversions of Estrogens.- References.- 3 Non-steroidal Estrogens.- A. Introduction.- B. Structural Classifications of Non-Steroidal Estrogens.- I. 1,2-Diarylethanes and Ethylenes.- 1. Diethylstilbestrol (DES), hexestrol (HES) and Analogs.- 2. Structure — Activity Relationships.- 3. DES Metabolites.- II. Flavones and Isoflavones.- III. Macrolactones.- IV. Alkylphenols and Arylphenols.- V. Non-Aromatic Estrogens.- VI. Miscellaneous Non-Steriodal Templates.- C. Conclusions.- References.- 4 Antiestrogens and Partial Agonists.- A. Introduction.- B. Triphenylethylene Derivatives.- I. Tamoxifen.- II. Triphenylethylene Derivatives Related to Tamoxifen.- III. Fixed-Ring Analogues of Tamoxifen.- IV. 1,2,3-Triarylpropenone-Derived Antiestrogens.- C. Diphenylethylene Derivatives.- I. 1,1-Diphenylethylene-Derived Agents.- II. 1,2-Diphenylethylene Derivatives.- III. 2-Phenylindoles and Related Heterocycles.- D. Steroidal Compounds.- I. 7?-Substituted Estradiol Derivatives.- II. 11?-Substituted Estradiol Derivatives.- E. Conclusion.- References.- 5 Structure — Activity Relationships.- A. Introduction.- B. Estrogens and Antiestrogens with a Modified Steroid Structure.- I. Modifications of the A Ring.- II. Modifications of the D Ring.- III. Modifications of the B Ring.- IV. Modifications of the C Ring.- V. Conclusion.- C. Non-Steroidal Estrogens and Antiestrogens.- I. Derivatives of Diethylstilbestrol.- II. 2-Phenylindole Derivatives.- III. 2-Phenylbenzo[b]thiophene Derivatives.- IV. Triphenylethylene Derivatives.- V. 2,3-Triphenyl-2H-1-Benzopyrans and Related Structures.- VI. Conclusion.- References.- 2: Molecular Biology of Estrogenic Action.- 6 Structure and Function of the Estrogen Receptor.- A. Introduction.- B. Structure of the Estrogen Receptor.- I. The A/B Domain.- II. The DNA-Binding Domain.- III. The Ligand-Binding Domain.- C. ER Functions and Transcription.- I. ER DNA-Binding Properties.- IL ER Ligand-Independent Activity.- III. Ligand-Dependent Transcriptional Activity.- D. ER Isotype Diversity Generates Specificity.- I. ERa and ER/? Heterodimerization.- II. Tissue Distribution and Ligand Binding.- III. ERa and ER/? Differential Activity.- E. ERa Knock-Out Mouse: A Functional Model.- F. Future Directions.- References.- 7 Estrogen-Regulated Genes.- A. Introduction.- B. Transcriptional Control of Gene Activity by Estrogens.- I. Molecular and Cellular Determinants of Gene Responses to Estrogens.- 1. The Estrogen Receptors.- 2. Estrogen-Reponsive Gene Elements.- a) Estrogen Response Elements and Other Estrogen-Responsive DNA Elements.- b) Target Gene Promoters.- 3. The Target Cell Environment.- C. Non-transcriptional Control of Gene Activity by Estrogens.- I. Post-transcriptional Effects of Estrogens.- II. Extra-Genomic Effects of Estrogens.- References.- 8 Regulation of Constitutive and Inducible Nitric Oxide Synthase by Estrogen.- A. Introduction.- B. Isoenzymes of NOS.- I. Nitric Oxide Synthase-I.- IL Nitric Oxide Synthase-II.- III. Nitric Oxide Synthase-III.- C. Regulation of NOS Isoenzymes by 17?-Estradiol.- I. Inhibition of NOS-II Activity by 17?-Estradiol.- II Upregulation of Endothelial NOS-III Activity by 17?-Estradiol.- 1. Gender Difference and the Effect of 17?-Estradiol on Endothelial Function.- 2. Potential Mechanism of Estrogen-Induced Increased Endothelial NO Production.- a) NOS-III Gene Expression.- b) NOS-III Enzyme Activity.- c) Bioactivity of NO.- 3. Role of the Estrogen Receptor in the Regulation of NOS-III.- 4. Role of Increased Endothelial NO in the Anti-Atherosclerotic Effect of 17?-Estradiol.- D. Summary.- References.- 9 Non-Genomic Effects of Estrogens.- List of Abbreviations.- A. Introduction.- B. Evidence for Fast Estradiol-Evoked Biological Responses.- I. Central Biological Responses.- 1. Fast Estradiol Effects on the Catecholamine System.- 2. Fast Estradiol Effects on the Hippocampus.- 3. Fast Estradiol Effects on Other Areas of the Central Nervous System.- II. Peripheral Biological Responses..- C. Evidence for Specific Estradiol Binding Sites in Cellular Membranes.- I. Central Sites.- II. Peripheral Sites.- D. Evidence for Diverse Protein Estrogen Binders.- I. Estrogen Binders in Plasmalemmal Microsomal Fractions.- II. Estrogen Binders in Mitochondrial Lysosomal Fractions.- III. Estrogen Binders from Other Origins.- E. Diverse Mechanisms in the Fast Actions of Estradiol.- I. Channel Regulator.- 1. Ca2+ Channels.- 2. Others.- II. Transduction Activator.- 1. Cyclic Adenosine Monophosphate (cAMP).- 2. Phospholipase C (PLC).- 3. Mitogen-Activated Protein Kinase (MAPK).- III. Metabolic Regulator.- 1. ATPase/ATP Synthase.- 2. Glyceraldehyde-S-Phosphate Dehydrogenase (G3PD).- 3. Others.- F. Overview and Concluding Remarks.- I. The Continuum Theory.- References.- 10 Molecular Mechanisms of Antiestrogen Action.- A. Introduction.- B. Key Elements in Estrogen-Receptor Signalling Important for Antiestrogen Action.- C. Molecular Actions of Antiestrogens.- I. Effects of Antiestrogens on Binding to the Receptor, Dimerisation and Nuclear Localisation.- II. Effects of Antiestrogens on Estrogen Receptor (ER) — Estrogen Response Element (ERE) Binding and Subsequent Transcriptional Activation.- 1. Altered ER — ERE Binding Efficiency.- 2. Changes in ER Conformation Influence AF-2 Activity.- 3. Effects Enabled by AF-1 and the Phenomenon of AF-1/AF-2 Promoter Dependency.- 4. Effects Enabled by the Cellular Levels of Co-Activators/Co-Repressors.- 5. Effects on Ligand-Independent ERE Transactivation.- 6. Effects Enabled by Promoter Elements and ERE Sequence.- 7. Effects Enabled by ER Sub-Type.- III. Effects on Ap-1- and NF-kB-Mediated Transactivation.- IV. Effects on Antiestrogen-Specific Response Elements.- V. Effects on ER Degradation.- VI. Non-ER Action of Antiestrogens.- D. Modifying Effects of the Normal Cellular Phenotype on Antiestrogen Response.- E. Modifying Effects of the Cancer Cell Phenotype on Antiestrogen Response.- F. Conclusions.- References.- 3: Biosynthesis and Metabolism of Endogenous Estrogens.- 11 Estrogen Transforming Enzymes.- A. Introduction.- B. Metabolism of Estradiol by 17?-Hydroxysteroid Dehydrogenase Type 2 (HSD2).- I. 17?HSD Superfamily.- II. Tissue Distribution.- III. Regulation of 17?HSD2.- C. Cytochrome P450 Mono-Oxygenase Hydroxylation of Estrogens.- I. Cytochrome P450s.- II. C2-and C16?-Hydroxylation of Estrogens.- 1. Effect of 2- or 16?-Hydroxylation on Metabolite Estrogenicity.- 2. Modulation by Thyroid Hormones, Body Weight and Diet.- 3. Effect of Smoking on C2/C16?-Hydroxylation.- 4. C2/C16?-Hydroxylation and Breast Cancer.- 5. Induction of C2-Hydroxylation by Indole-3-Carbinol.- 6. C2/C16?-Hydroxylation in Different Ethnic Groups.- 7. Effect of Pesticides on C2/C16?-Estrogen Hydroxylation.- 8. Inhibition of C2-Hydroxylation.- 9. Estrogen-2-Hydroxylation by Placental Aromatase.- D. Catechol Estrogens and Carcinogenesis.- E. Estrogen Sulphates.- I. Estrogen Sulphate Formation.- II. Biological Role of Estrogen Sulphation.- III. Regulation of Estrogen Sulphation.- F. Estrogen Glucuronides.- G. Lipoidal Estrogens.- H. Conclusions.- References.- 12 Metabolism of Endogenous Estrogens.- A. Introduction.- I. Estradiol Breakdown Mechanisms.- II. Sex Differences in Estradiol Metabolism.- III. Catechol Estrogen Metabolism.- B. Estrogen Metabolism and Disease.- I. Breast Cancer.- II. Endometrial Cancer.- III. Cervical Cancer.- IV. Prostate Cancer.- V. Papilloma of the Larynx.- VI. Liver Disease.- VII. Lupus Erythematosus.- VIII. Disease of the Thyroid.- IX. Weight Changes.- X. Depression.- XL Osteoporosis.- C. Drugs.- D. Lifestyle.- E. Pregnancy.- I. Changes in Metabolism During Pregnancy.- References.- 4: Physiology and Pathophysiology of Estrogens.- 13 Phylogeny of Estrogen Synthesis, Extragenital Distribution of Estrogen Receptors and Their Development Role.- A. Phylogeny of Estrogen Synthesis.- B. Extragenital Distribution of Estrogen Receptors and Their Functional Significance.- I. Breast.- II. Bone.- III. Gastrointestinal Tract.- IV. Cardiovascular System.- V. Immune System.- VI. Pituitary.- VII. Central Nervous System.- VIII. Membrane-Bound ERs.- C. Hormonal Regulation of ER Synthesis.- I. Estrogens.- II. Thyroid Hormones.- III. Progesterone.- IV. Androgens.- V. Glucocorticoids.- VI. Neurotransmitters.- D. Developmental Role of ERs as Exemplified by Hormone-Dependent Brain Differentiation.- References.- 14 Female Reproductive Tract.- A. Embryology of the Reproductive Tract.- B. Sex Differentiation.- I. Genetic Sex.- II. Gonadal Sex.- 1. Male.- 2. Female.- III. Somatic Sex.- 1. Male Sex Differentiation.- 2. Female Sex Differentiation.- 3. Estrogens and Sex Differentiation.- C. Estrogens and Ovary.- D. Fallopian Tubes.- I. Steroidal Regulation.- E. Uterus.- I. Estrogen Regulation.- II. Estrogens and Uterine Pathology.- F Cervix.- I. Estrogen Regulation.- G. Vagina.- I. Estrogens and Vaginal Pathology.- References.- 15 Estrogen and Brain Function: Implications for Aging and Dementia.- List of Abbreviations.- A. Introduction.- B. Current Views on Estrogen’s Mechanism of Action.- C. Non-Reproductive Brain Functions Influenced by Estrogen.- I. Cognition (Learning and Memory).- 1. Basal Forebrain Cholinergic System.- 2. Hippocampal ?-Aminobutyric Acid (GABA) Interneurons.- 3. Hippocampal CA1 Pyramidal Neurons.- II. Psychological Function.- 1. Midbrain Serotonergic Neurons.- III. Sensorimotor Performance.- 1. Nigrostriatal Dopaminergic System.- IV. Non-Neuronal Functions: “Brain Maintenance”.- 1. Glial Cells.- 2. Endothelial Cells of the Blood — Brain Barrier (BBB).- D. Summary.- References.- 16 Cardiovascular System.- A. Introduction.- B. Cardioprotective Mechanism of Estrogens.- I. Indirect Action on the Cardiovascular System by a Change of the Lipid Balance.- 1. Atherogenic Lipoproteins.- 2. High-Density Lipoprotein.- 3. Lipoprotein (a).- 4. Influence of Estrogen Replacement Therapy and HRT on the Lipid Profile.- II. Direct Effect of Estrogens on the Vascular Wall.- C. Influence of Progesterone and Progestagens.- D. Conclusion.- References.- 17 Immune System.- A. Introduction.- B. Effect on Primary Lymphoid Tissue.- I. The Effect of Estrogens.- 1. The Bone Marrow.- 2. The Thymus.- C. Effect on Immune Function.- I. The Effect of Estrogens.- 1. Receptors.- 2. Cytokines.- 3. Humoral Immunity.- 4. Cell-Mediated Immunity.- 5. Inflammation.- II. The Effect of Anti-Estrogens.- 1. Lymphocytes.- 2. Humoral Immunity.- 3. Cell-Mediated Immunity.- 4. Inflammation.- D. Conclusions.- References.- 18 Male Reproductive function.- A. Introduction.- B. Source of Estrogen in the Male.- C. Localization of the Estrogen Receptor in the Male Genital Tract.- D. Function of Estrogens in the Male.- I. Bone Maturation.- II. Testicular Function.- III. Prostate.- IV. Behavior.- E. Conclusions.- References.- 19 The Effect of Estrogens and Antiestrogens on the Urogenital Tract.- A. Introduction.- B. Pathophysiology.- I. Hormonal Influences on the Urogenital Tract.- II. The Effect of Ageing on the Bladder.- C. Estrogen and Urinary Incontinence.- I. Epidemiological Studies.- II. Estrogen and the Continence Mechanism.- III. Estrogens for Stress Incontinence.- IV. Estrogens for Urge Incontinence.- D. Estrogen for Recurrent Urinary-Tract Infections.- E. Estrogen for Vaginal Atrophy.- E Antiestrogens and the Urogenital Tract.- G. Conclusions.- References.- 20 Effects of Estrogens on Various Endocrine Regulations.- A. The Complexity of Estrogen’s Action on Various Tissues.- I. Introduction.- II. Estrogen Receptor-Mediated Tissue Specificity.- III. Sex-Hormone-Binding Globulin-Mediated Estrogenic Action.- B. Estrogens and the Thyroid.- I. Sexual Dimorphism in Thyroid Disease.- II. The Effect of Estrogens in Thyroid Enlargement.- III. Thyroid Dysfunction.- IV Thyroid Hormone-Binding Globulin.- V Thyrotropin Regulation.- C. Estrogens and the Adrenal Glands.- I. Sexual Dimorphism in Adrenal Disease?.- II. Regulation of Adrenal Sex-Steroid Precursors.- III. Anti-toxic Properties of the Adrenal Glands.- IV Corticosteroid-Binding Globulin.- V Corticotropin Regulation.- D. Estrogens and the Phosphocalcic Metabolism.- I. Bone Remodeling and Calcium Kinetics.- II. Parathyroid Hormone.- III. Vitamin D.- References.