The Prostaglandins: v. 2

There is much evidence to suggest that prostaglandins may have a physiological role to play in the control of thyroid gland metabolism, although the precise nature of this role remains to be defined. Prostaglandins have been found in normal thyroid tissue, and there is evidence of increased levels in some, but not all, cases of medullary carcinoma of the thyroid. which may account for the associated diarrhea. Exogenous prostaglandins, like TSH, bind to thyroid plasma mem- branes, stimulate the adenylate cyclase-cyclic AMP system, thyroid hormone secretion, iodide organification, colloid droplet formation, glucose oxidation, and 32p incorporation into phospholipids. Prosta- glandins of the E series are the most potent, although their maximal effects are generally less than the maximal effects of TSH. The interrelationships existing between TSH and prostaglandins have been the subject of intensive investigation, but as yet no one uni- fying concept has emerged. TSH and prostaglandins have been shown to occupy different receptors on the thyroid plasma membrane. Al- though TSH can increase intracellular prostaglandin levels, probably as a result of increased synthesis, prostaglandins do not appear to be essential intermediates in TSH action on adenylate cyclase. The pos- sibility that prostaglandins are part of a negative feedback system con- trolling TSH action is, as yet, a tentative hypothesis, and further work will be required to unravel the interrelationships between these sub- stances that now appear to be far more complex than has been envisaged thus far.

Table of Contents:
1 Aspirin and Prostaglandins.- I. Introduction.- II. Inhibition of Prostaglandin Synthetase from Different Species and Tissues by Nonsteroid Anti-Inflammatory Agents.- A. Absolute Potencies.- B. Relative Potencies.- III. Relationship between Potency of Aspirin-Like Drugs Against Prostaglandin Synthetases In Vitro and Anti-Inflammatory Activity.- A. Variations in Potency.- B. Drug Concentrations in Plasma.- IV. Contribution of Prostaglandins to the Inflammatory Process.- A. Prostaglandin Release.- B. Release of Chemical Mediators.- C. Possible Control Mechanisms for Prostaglandin Biosynthesis and Release.- D. Inflammatory Effects of Prostaglandins.- V. Relationship between In Vivo Inhibition of Prostaglandin Generation and Therapeutic Effects of Nonsteroid Anti-Inflammatory Drugs.- VI. Side-Effects of Nonsteroid Anti-Inflammatory Agents.- VII. Use of Nonsteroid Anti-Inflammatory Drugs as a Test for the Involvement of Prostaglandins in Some Biological Systems.- A. Intestinal Smooth Muscle Tone.- B. Contractions of the Uterus.- C. Contribution of Prostaglandins to Ovary Function.- D. Control of Lipolysis.- E. Control of Release of the Sympathetic Mediator.- F. Local Regulation of Blood Flow.- VIII. Conclusions.- IX. References.- 2 The Thyroid Gland.- I. Introduction.- II. Occurrence and Synthesis of Prostaglandins in the Thyroid.- A. Normal Thyroid.- B. Medullary Carcinoma of the Thyroid.- C. Prostaglandin Synthesis in the Thyroid.- III. Effects of Prostaglandins on Thyroid Gland Metabolism.- A. The Adenylate Cyclase-Cyclic AMP System.- B. Iodine Metabolism and Thyroid Hormone Secretion.- C. Glucose Oxidation.- D. 32P Incorporation into Phospholipid.- E. Conclusions.- IV. Interrelationships of Prostaglandins and TSH.- A. Prostaglandin Analogues.- B. Combined Actions of Prostaglandins and TSH.- C. Dissociation of TSH and Prostaglandin Effects.- D. Conclusions.- V. Summary.- VI. References.- 3 The Mature Erythrocyte.- I. Introduction.- II. Prostaglandins in the Erythrocyte.- A. Synthesis and Release.- B. Metabolism and Inactivation.- C. Binding.- D. Uptake and Distribution.- III. Action on the Mechanical Properties of the Red Cell.- A. Deformability.- B. Hemolysis.- IV. Effects on Obligatory Cation Exchange.- A. Monovalent Cations.- B. Divalent Cations.- V. Metabolic Effects of Prostaglandins.- A. ATP and A TP-Regulating Enzymes.- B. Cyclic AMP.- VI. Effects on Hemoglobin.- VII. Implications in the Pathological State.- VIII. Prostaglandin Antagonists.- IX. Use of Prostaglandins in Preparation and Storage of Plasma Concentrates.- XI. Conclusions.- XI. References.- 4 Prostaglandin Dehydrogenase.- I. Introduction.- II. Metabolic Deactivation.- III. PGDH Distribution.- IV. Enzyme Purification.- A. Requirements.- B. Methods.- C. Assays for PGDH Activity.- V. Some Properties of the Purified PGDH.- A. Purity.- B. Stability.- C. Molecular Weight.- D. pH.- E. Coenzyme.- F. Substrate Activity.- VI. Characteristics of Binding to PGDH.- A. The PG Site.- B. Comparison with Receptors for the Biological Actions of PGs.- C. The DPN+ Site.- VII. Reversibility of PGD.- VIII. Other Regulatory Factors.- IX. Enzymatic Assay of PGs.- X. Summary.- XI. References.- 5 Behavioral Effects.- I. Introduction.- II. Role of Prostaglandins in Brain Function.- III. Role of Prostaglandins in Neurotransmission.- IV. Metabolism of Prostaglandins in Brain.- V. Effects of Prostaglandins on Behavior.- VI. Effects of Prostaglandins on Body Temperature.- VII. Summary and Conclusions.- VIII. References.- 6 Embryonic and Fetal Development.- I. Introduction.- II. Action on the Early Conceptus.- A. Laboratory Animals.- B. Human Studies.- III. Teratogenicity Studies.- A. Teratogenic Influences.- B. Mammalian Species.- C. Chick Development.- D. Congenital Anomalies.- IV. Fetal Effects in Humans.- V. Prostaglandin-Progesterone Effects.- VI. Prostalandin-Synthetase Inhibitors.- VII. Prostaglandins and the Placenta.- A. Functional.- B. Morphological.- VIII. Conclusions.- IX. References.- 7 Search for Common Mechanisms Underlying the Various Effects of Putative Inflammatory Mediators.- I. Introduction.- II. Historical Background.- III. Actions of and Interactions Between Potential Mediators and Drugs.- A. Introduction.- B. Rat Paw Edema: Mechanisms of Induction and Inhibition and Hypothesized Role of Phospholipase A2.- C. Edema and Vascular Permeability Increase by Venoms.- D. Ultraviolet Erythema in Guinea Pigs and Lipoperoxidation during Inflammation.- E. Direct and Indirect Effects of Bradykinin.- F. Effects of Adenosine Nucleotides.- G. Effects of Arachidonic Acid and of Slow-Reacting Substance C.- H. Pharmacological Properties of a Few Substances Known to Induce Inflammation.- IV. Evidence from Studies on Anti-Inflammatory Drugs in Isolated Cell Systems.- A. Erythrocytes.- B. Mast Cells.- C. Platelets.- V. Summary and Conclusions.- VI. References.- 8 Immunology.- I. Introduction.- II. IgE-Mediated Release of Histamine and Other Mediators.- III. Lymphocyte Cytolytic Activity.- IV. The Humoral Antibody Response.- V. Neutrophil and Macrophage Function.- VI. Lymphocyte Proliferation.- VII. Speculation on Prostaglandins and the Immune Response.- VIII. References.- IX Site-Directed Mutagenesis.- Appendix A UV Spectral Characteristics and Acidic Dissociation Constants of Modified Bases, Nucleosides, and Nucleotides.- Appendix B Acid, Neutral, and Basic Spectra of Bases, Nucleosides, Nucleotides, and 55 Modified Derivatives.