Uterine Function

1. Ultrastructure and Calcium Stores in the Myometrium.- 1. Introduction.- 2. Myometrium.- 3. Smooth Muscle Ultrastructure.- 3.1. Sarcolemma.- 3.2. Contractile Apparatus.- 3.3. Intracellular Structures.- 4. Cellular Calcium Stores.- 4.1. Sarcoplasmic Reticulum.- 4.2. Mitochondria.- 4.3. Sarcolemma.- 5. Conclusions.- References.- 2. Uterine Metabolism and Energetics.- 1. Introduction.- 2. Myometrial Metabolism and Energetics: An Overview.- 2.1. Contraction.- 2.2. Metabolic Recovery.- 2.3. Kinetics, Thermodynamics, and Cellular Compartmentation.- 2.4. Summary.- 3. Methods—Past, Present, and Possible.- 3.1. Noninvasive Methods.- 3.2. Heat Production.- 3.3. Oxygen Consumption.- 3.4. Fluorescence.- 3.5. Nuclear Magnetic Resonance Spectroscopy.- 4. Bioenergetically Important Metabolites in the Uterus.- 4.1. Concentrations of Phosphorus Metabolites.- 4.2. Alterations during Pregnancy and Parturition.- 4.3. Intracellular pH in the Myometrium.- 4.4. Myometrial Free Magnesium.- 4.5. Hormonal Control of Phosphorus Metabolite Levels.- 4.6. Effects of Disease.- 5. In Vivo Control of Function and Metabolism in the Myometrium.- 5.1. Comparison of Phosphorus Metabolites of Myometrium and Striated Muscles.- 5.2. Creatine Kinase.- 5.3. Energetics of Contraction.- 5.4. Economy and Efficiency of Contraction.- 5.5. Metabolism.- 6. Summary and Conclusions.- References.- 3. Myosin Light Chain Phosphorylation in Uterine Smooth Muscle.- 1. Introduction.- 2. Myosin.- 2.1. Historical Notes.- 2.2. Structure and Function.- 2.3. Isolation of Myosin.- 2.4. Myosin—Actin Interaction.- 3. Phosphorylation—Dephosphorylation.- 4. Isoforms of the 20-kDa Light Chain.- 5. Quantitation of Light Chain Phosphorylation.- 6. Light Chain Phosphorylation in Uterine Smooth Muscle.- 6.1. Spontaneous Activity.- 6.2. Drug-Induced Contraction.- 6.3. Drug-Induced Relaxation.- 6.4. Stretch Activation.- 7. Concluding Remarks.- References.- 4. Thin Filament Control of Uterine Smooth Muscle.- 1. Introduction.- 2. Location of Thin Filaments in the Contractile Matrix.- 3. Protein Components of the Thin Filament.- 3.1. Actin.- 3.2. Tropomyosin.- 3.3. Caldesmon.- 3.4. Native Thin Filament.- 4. Function of the Thin Filaments in Uterine Muscle Contraction.- 4.1. Native Thin Filaments plus Myosin.- 4.2. Actin plus Myosin.- 4.3. Actin—Tropomyosin plus Myosin.- 4.4. Actin—Tropomyosin—Caldesmon plus Myosin.- 4.5. Actin—Tropomyosin—Caldesmon with Calmodulin plus Myosin.- 4.6. The Ca2+-Binding Component of Native Thin Filaments.- 5. A Consensus Model for the Ca2+ Regulatory Mechanism in Smooth Muscle Thin Filaments.- 6. Physiological Role for Ca2+ Regulation of Thin Filaments.- 7. Conclusion.- References.- 5. Calcium Control Mechanisms in the Myometrial Cell and the Role of the Phosphoinositide Cycle.- 1. From Excitation to Contraction.- 2. Calcium as Activator of Contraction.- 2.1. Intracellular Calcium.- 2.2. Sources of Calcium and Calcium Transport.- 3. Uterine Muscle-Specific Problems.- 3.1. Microsomal Preparations.- 3.2. Criteria for Purity.- 3.3. Specific Markers.- 3.4. Molecular Parameters.- 4. Calcium Pumps and Relaxation.- 4.1. Plasma Membrane.- 4.2. Sarcoplasmic Reticulum.- 5. Rise of Intracellular Calcium and Contraction.- 5.1. Calcium Entry from the Extracellular Fluid.- 5.2. Calcium Release Mechanisms from the Sarcoplasmic Reticulum...- 5.3. Hormonal Effects on Intracellular Calcium Storage.- 5.4. Inhibition of Calcium Efflux.- 6. Pharmacomechanical Coupling.- 7. The Phosphoinositide System and Release of Second Messengers.- 7.1. Occurrence, Structure, and Metabolism.- 7.2. Inhibitors of the Phosphoinositide Cycle.- 7.3. Biological Function of the Phosphoinositides.- 7.4. Other Inositol Phosphates.- 7.5. Diacylglycerol.- 7.6. The Regulatory Role of Guanine Nucleotides.- 8. Summary and Conclusions.- References.- 6. Calcium Channels: Role in Myometrial Contractility and Pharmacological Applications of Calcium Entry Blockers.- 1. Introduction.- 2. Calcium Channels.- 2.1. General Properties.- 2.2. Selectivity.- 2.3. Channel Type.- 2.4. Modulation of Calcium Channels.- 3. Calcium Entry Blockers.- 3.1. Localization of Ligand Binding Sites.- 3.2. Characterization of Ligand Binding Sites.- 3.3. Alternative Sites of Action.- 3.4. Pharmacology.- 3.5. Pharmacokinetics.- 4. Effects of Calcium Entry Blockers on the Female Genital Tract.- 4.1. In Vitro Studies.- 4.2. In Vivo Studies.- 5. Summary.- References.- 7. The Role of Membrane Potential in the Control of Uterine Motility.- 1. Introduction.- 2. Origins of Membrane Potential.- 2.1. Generation of Ionic Gradients.- 2.2. Distribution of Ions in Smooth Muscle.- 2.3. Equilibrium Potentials in Smooth Muscle.- 3. Membrane Permeability and Passive Electrical Properties.- 3.1. Membrane Permeability.- 3.2. Passive Electrical Properties.- 3.3. Effect of Reproductive State on Passive Electrical Properties.- 4. Changes in Membrane Permeability and Active Responses.- 4.1. Mechanism of Ion Permeation.- 4.2. Excitability.- 4.3. Ion Channels in Smooth Muscle.- 4.4. Modulation of Channel Activity.- 5. Electrical Activity in the Myometrium.- 5.1. Pacemaker Potentials.- 5.2. Simple Action Potentials.- 5.3. Complex Action Potentials.- 5.4. Relationship between Membrane Potential and Contraction.- 5.5. Factors Affecting the Action Potential.- 6. Spread of Excitation.- 6.1. The Syncytial Nature of Smooth Muscle and Cell-to-Cell Coupling.- 6.2. Spread of Activity throughout the Uterus.- 7. Studies in Vivo.- 7.1. Pattern of Activity throughout Pregnancy.- 7.2. Comparison between Observations in Vivo and in Vitro.- 8. Concluding Remarks.- References.- 8. ?-Adrenoceptors, Cyclic AMP, and Cyclic GMP in Control of Uterine Motility.- 1. ?-Adrenoceptors and Cyclic AMP in Uterine Relaxation.- 1.1. Adrenergic Receptors in the Uterus.- 1.2. Coupling of Adrenergic Receptors to Adenylate Cyclase.- 1.3. Evidence for and against a Role for cAMP as a Mediator of Uterine Relaxation.- 2. Role of Cyclic GMP in Control of Uterine Motility.- 2.1. Cyclic GMP as a Possible Mediator of Uterine Contraction.- 2.2. Cyclic GMP as a Possible Mediator of Uterine Relaxation.- 3. Use of ?-Adrenoceptor Agonists in Premature Labor.- 4. Summary and Conclusions.- 4.1. ?-Adrenoceptors and cAMP in Uterine Relaxation.- 4.2. Role of cGMP in Control of Uterine Motility.- 4.3. Use of ? -Adrenoceptor Agonists in Premature Labor.- References.- 9. Physiological Roles of Gap Junctional Communication in Reproduction.- 1. Introduction.- 2. Functional Implications of Junctional Communication.- 3. Structural and Functional Studies of Uterine Gap Junctions.- 3.1. Uterine Endometrium.- 3.2. Uterine Myometrium.- 3.3. Uterine Serosal Epithelium.- 4. Conclusions.- References.- 10. Molecular Mechanisms of Steroid Hormone Action in the Uterus.- 1. Introduction.- 2. Historical Perspective.- 3. Biochemical Studies.- 3.1. Receptor Proteins in Target Cells.- 3.2. Receptor Transformation.- 3.3. Intracellular Localization.- 3.4. Current Status of the “Two-Step” Mechanism.- 3.5. Receptor Phosphorylation.- 4. Immunochemical Studies.- 4.1. Antibodies to Estrogen Receptor.- 4.2. Antibodies to Progestin Receptor.- 5. Molecular Biological Studies.- 5.1. Receptor Cloning and Structure.- 5.2. Interaction with Target Genes.- 6. Summary.- References.- 11. Oxytocin in the Initiation of Labor.- 1. Synthesis and Secretion of Oxytocin.- 2. Oxytocin in Animal Parturition.- 3. Maternal Oxytocin in Human Parturition.- 3.1. Plasma Oxytocin Levels.- 3.2. Oxytocin Plasma Clearance Rate.- 3.3. Oxytocin in the Corpus Luteum.- 3.4. Cerebrospinal Fluid Oxytocin.- 3.5. Labor in Hypophysectomized Women.- 3.6. Labor Facilitation by Oxytocin.- 4. Special Considerations in Measuring Plasma Oxytocin.- 5. Placental Transfer of Oxytocin.- 6. Fetal Oxytocin in Labor.- 6.1. Fetal Oxytocin in Animal Parturition.- 6.2. Fetal Oxytocin in Human Parturition.- 7. Conclusion.- References.- 12. Oxytocin Receptors in the Uteru.- 1. Introduction.- 2. The Relationship between Sensitivity and Oxytocin Receptors.- 3. Criteria for Oxytocin Binding Sites Being Receptors.- 4. Methods for Determining Oxytocin Receptor Concentrations.- 5. Myometrial Oxytocin Receptor Regulation.- 5.1. Steroids.- 5.2. Metal Ions and Oxytocin Action.- 5.3. Oxytocin Analogues and Metal Ions.- 6. Distinct Vasopressin and Oxytocin Receptors in the Myometrium of Nonpregnant Women.- 7. Characterization of Oxytocin Binding Sites.- 7.1. Solubilization of Oxytocin Receptors.- 7.2. Information Gained from the Use of Oxytocin Analogues.- 8. Coupling between Oxytocin-Receptor Occupancy and Cell Contraction.- 8.1. Calcium.- 8.2. Calcium, Magnesium ATPase.- 8.3. Phosphoinositol Metabolism.- 8.4. Lack of Evidence for Involvement of a G Protein.- 9. Endometrium.- 9.1. Endometrial Oxytocin Receptors.- 9.2. Effects of Oxytocin on Endometrial Prostaglandin Synthesis.- 10. Concluding Remarks.- References.- 13. Regulatory Peptides and Uterine Function.- 1. Introduction.- 2. Peptide Biosynthesis.- 3. Vasoactive Intestinal Peptide and Peptide with N-Terminal Histidine and C-Terminal Isoleucine Amide.- 3.1. Localization.- 3.2. Biological Action.- 3.3. Functional Significance.- 4. Neuropeptide Y.- 4.1. Localization.- 4.2. Biological Action.- 4.3. Physiological Implications.- 5. Substance P.- 5.1. Localization.- 5.2. Biological Action.- 5.3. Physiological Implications.- 5.4. Labor.- 6. Enkephalins: Leu- and Met-Enkephalin.- 6.1. Localization.- 6.2. Biological Action.- 7. Calcitonin-Gene-Related Peptide.- 7.1. Localization.- 7.2. Biological Action.- 8. Galanin.- 9. Oxytocin, Vasopressin, Renin, and Relaxin.- 10. Somatostatin.- 11. Conclusion and Perspectives.- References.- 14. Biosynthesis and Function of Eicosanoids in the Uterus.- 1. History of Prostaglandins.- 2. Isolation and Structure of Prostaglandins.- 3. Arachidonic Acid Metabolism.- 4. Cyclooxygenase Pathways of Arachidonic Acid Metabolism.- 4.1. Prostacyclin.- 4.2. Thromboxanes.- 4.3. Prostaglandins D2, E2, and F2a.- 5. Lipoxygenase Pathways of Arachidonic Acid Metabolism.- 6. Control of Eicosanoid Biosynthesis in the Uterus.- 6.1. Control of Prostaglandin Biosynthesis in the Uterus.- 6.2. Synthesis of Lipoxygenase Products by the Uterus.- 7. Prostaglandin and Leukotriene Receptors.- 8. Prostaglandin Contractile Action on the Cellular Level.- 9. Prostaglandin and Oxytocin Interaction.- 10. Role of Prostaglandins in Tubal Motility.- 11. Role of Prostaglandins and Leukotrienes as Mediators of Decidualization.- 12. Prostaglandins and the Intrauterine Contraceptive Device.- 13. Menorrhagia.- 14. Prostaglandins and Endometriosis.- 15. Cervical Ripening.- 16. Conclusion.- References.- 15. Pharmacological Application of Prostaglandins, Their Analogues, and Their Inhibitors in Obstetrics.- 1. Introduction.- 2. Termination of Pregnancy.- 2.1. Mechanism.- 2.2. Early Pregnancy Termination.- 2.3. Midtrimester Pregnancy Termination.- 2.4. Pregnancy Termination in Abnormal Pregnancy.- 2.5. Current Use of Prostaglandins.- 2.6. Cervical Priming.- 3. Term Cervical Ripening and Induction of Labor.- 3.1. Physiological Background.- 3.2. Prostaglandin E2 for Cervical Ripening.- 3.3. Prostaglandin E2 Preparations for Local Application.- 3.4. Present Status of PGE2 Use for Induction of Labor.- 4. Postpartum Hemorrhage.- 4.1. Use of PGF2?.- 4.2. Use of Analogues of PGF2a.- 4.3. Use of PGE2.- 5. Inhibition of Preterm Labor with Prostaglandin Synthetase Inhibitors.- 5.1. Efficacy of Indomethacin.- 5.2. Side Effects of Indomethacin.- 6. Conclusions.- References.- 16. Fetal Tissues and Autacoid Biosynthesis in Relation to the Initiation of Parturition and Implantation.- 1. Introduction.- 2. Autacoids in Amniotic Fluid.- 2.1. Prostaglandins.- 2.2. Platelet-Activating Factor.- 3. Tissue Origins of Autacoids Found in Amniotic Fluid in Association with Parturition.- 3.1. Fetal Membranes.- 3.2. Other Fetal Tissues as Sources of PAF and Prostaglandins.- 4. Enzymatic Synthesis and Degradation of Autacoids during Parturition.- 4.1. Biosynthesis of Prostaglandins in Fetal Membranes.- 4.2. Biosynthesis of PAF in Amnion Tissue.- 4.3. Biosynthesis of PAF in Fetal Lung.- 4.4. Maternal Plasma PAF AcetyIhydrolase Activity.- 5. Regulation of Autacoid Production during Parturition.- 5.1. Calcium.- 5.2. Positive and Negative Effectors.- 5.3. Cyclic AMP.- 6. Functional Significance of Autacoid Production during Parturition.- 6.1. Myometrial Contraction.- 6.2. Lung Maturation.- 6.3. Preterm Labor.- 7. Early Pregnancy.- 8. Conclusion.- References.- 17. Endocrinology of Pregnancy and Parturition.- 1. Overview.- 2. Hypotheses.- 3. Endocrinology of Pregnancy and Parturition in Sheep.- 4. Endocrinology of Pregnancy and Parturition in Women.- 4.1. Introduction.- 4.2. The Human Fetal Adrenal.- 4.3. Estrogen.- 4.4. Progesterone.- 5. Endocrinology of the Fetal-Maternal Organ Communication System.- References.- 18. Circulation in the Pregnant Uterus.- 1. Vascular Anatomy.- 1.1. Nonpregnant.- 1.2. Pregnant.- 1.3. Experimental Animals.- 2. Methods for Study of Uterine Circulation and Blood Flow in the Human.- 2.1. Total Uterine Blood Flow.- 2.2. Placental Blood Flow.- 2.3. Other Methods.- 3. Physiology of Uterine Circulation.- 3.1. Neural Control.- 3.2. Autoregulation.- 3.3. Labor and Delivery.- 3.4. Hormonal Effects.- 4. Pathophysiology.- 4.1. Growth Retardation.- 4.2. Effects of Position.- 4.3. Hypertension.- 4.4. Smoking.- 4.5. Recreational Drugs.- 4.6. Exercise.- 5. Conclusions.- References.- 19. Effects of Obstetric Analgesia and Anesthesia on Uterine Activity and Uteroplacental Blood Flow.- 1. Introduction.- 1.1. Pressure—Flow Relationship of the Uterine Vascular Bed.- 1.2. Adrenergic Influences on Uterine Blood Flow and Uterine Activity.- 1.3. The Influence of Pregnancy and Labor on Sympathetic Nervous System Activity.- 1.4. Neural Reflexes and Uterine Activity.- 1.5. Influence of Maternal Respiratory and Acid-Base Status on Uterine Blood Flow.- 2. Local Anesthetics and Regional Analgesia.- 2.1. Direct Effects of Local Anesthetics on Uterine Activity and Uterine Blood Flow.- 2.2. Effects of Local Anesthetics Used for Pain Relief on Uterine Activity and Uterine Blood Flow.- 3. General Anesthesia and Sedation.- 3.1. Inhalation Anesthetics.- 3.2. Barbiturates.- 3.3. Ketamine.- 3.4. Narcotics.- 3.5. Sedative Tranquilizers.- 3.6. Neuromuscular Blocking Agents.- 3.7. Antihypertensive Agents.- 4. Summary.- References.