Steroid–Cell Interactions

Steroid–Cell Interactions describes the processes involved in the intracellular binding of steroids (and related compounds) in mammalian cells. Serum binding proteins and steroid-immunoglobulin interaction are also discussed, along with the relationship of these binding processes to the biological action of the steroid. This book consists of 10 chapters and begins by presenting an elementary account of the factors contributing to the interaction between a steroid hormone and another molecule. The discussion then turns to the three types of methods used to study the interaction between steroids and tissue receptors: cell fractionation, autoradiography, and the separation of specifically and non-specifically bound steroids. The next chapter deals with the metabolism of steroid hormones in relation to their binding and mechanism of action, focusing on testosterone and progesterone. The reader is also introduced to the intracellular binding of androgens, glucocorticoids, mineralocorticoids, and estrogens and to how binding is related to biological activity. The final chapter reviews the clinical and immunological data relevant to steroid-protein binding. This text will be of interest to students and practitioners of biology, biochemistry, and physiology.

Table of Contents:
Introduction1 Physico-Chemical Considerations of Steroid-Receptor Interactions Steroid Structure Reactant Groups Conformation Protein Structure Quaternary Structure Secondary and Tertiary Structure Primary Structure Nucleic Acids Chemical Bonds Covalent Bond Ionic Bond Hydrogen Bond Van der Waals' Forces Hydrophobic Bond General Comments Equilibrium Constant and Free Energy Measurement of Binding Constants Reaction Kinetics2 Methods Used to Study Steroid-Tissue Receptor Interaction Cell Fractionation Cell Type Mechanical Methods Cell Culture The Use of Tumors Autoradiography Distinction between High and Low Affinity Binding Sites3 The Importance of the Metabolism of Steroid Hormones Relative to Their Binding and Mechanism of Action The Absence of the Metabolism of Steroid Hormones During Their Uptake and Retention in Many Target Cells The Metabolism of Testosterone in Androgen-Dependent Tissues The Metabolism of Progesterone in Certain Target Tissues4 Androgens and Particularly, A Metabolite of Testosterone, 5a-Dihydrotestosterone Blood Blood Cells Plasma The Distribution of NADPH-Dependent 5a-Reductase and Receptors for 5a-Dihydrotestosterone in Androgen-Sensitive Tissues and Cells The Uptake of Testosterone into Androgen-Sensitive and Androgen-Dependent Tissues The Specific, High Affinity Binding of 5a-Dihydrotestosterone in the Rat Ventral Prostate Gland The Nuclear Binding of 5a-Dihydrotestosterone Cytoplasmic Binding of 5a-Dihydrotestosterone Development of Reconstituted Systems for the Transfer of 5a-Dihydrotestosterone into Nuclei or Chromatin, In Vitro Binding of Other Steroids in the Prostate Gland Binding of Testosterone Metabolites to Prostate Microsomes Summary Binding of 5a-Dihydrotestosterone in Accessory Sexual Glands Other than Rat Ventral Prostate Gland Experimental Animals Human Prostate Gland Searches for Receptors in Other Androgen-Sensitive Systems Liver Muscle Mouse Kidney Experimental Tumors Testis Binding of Androgens in Other Tissues and Cells Female Accessory Sexual Glands Brain Pseudomonas testosteroni and Other Bacteria General Summary5 Glucocorticoids Blood Blood Cells Plasma Specific Glucocorticoid Receptor Proteins Liver Uptake of Glucocorticoids into Rat Liver The Identification of Glucocorticoid-Protein Complexes in the Cytoplasm of Rat Liver Investigations on Steroid-Protein Complexes in Rat Liver Nuclei Summary HTC Cells Uptake of Dexamethasone into HTC Cells Nuclear Binding of Glucocorticoids Binding of Glucocorticoids in the Cytoplasm Interrelationship between the Cytoplasmic and Nuclear Receptors Summary HeLa Cells The Binding of Glucocorticoids in Intact HeLa Cells The Subcellular Distribution of Glucocorticoid Binding Sites Summary Lymphocytes The Uptake of Glucocorticoids into Lymphocytes Nuclear Receptor for Glucocorticoids Cytoplasmic Binding of Glucocorticoids The Probable Conversion of the Cytoplasmic Receptor into the Nuclear Receptor The Generality of the High Affinity Glucocorticoid-Binding Process in Lymphocytes Summary Lymphoid Tumors P1798 Tumors Lymphomas Summary Fibroblasts The Uptake of Glucocorticoids into Fibroblasts Characterization of the Cytoplasmic Binding Component The Receptor Content of Glucocorticoid-Resistant L929 Cells Summary Other Tissues Mammary Gland Brain General Summary6 Mineralocorticoids Blood Blood Cells Plasma The Search for Specific Aldosterone-Bindinq Proteins Rat Kidney The Nuclear Binding of Aldosterone The Cytoplasmic Binding of Aldosterone The Interrelationship between the Cytoplasmic and Nuclear Receptors The Binding of Other Steroid Hormones in Rat Kidney Summary Toad Bladder The Specificity and Characteristics of the Binding of Aldosterone Attempts at the Isolation of the Receptors Summary Other Tissues General Summary7 Estrogens Blood Formed Elements Plasma Entry of Estrogen into Cells Intracellular Distribution Uterus Cytoplasmic Binding Entry into the Nucleus Nucleus Loss of Estradiol from the Cell Uterine Cell Type Overall Picture of Estrogen Movement in the Cell Vagina Pituitary Gland Brain Autoradiography Biochemical Studies Neonatal Androgenization Ovary Kidney Prostate and Seminal Vesicle Oviduct Mammary Gland Tumors DMBA-Induced Rat Mammary Adenocarcinomas Other Rat Mammary Tumors Mouse Mammary Tumors Human Mammary Tumors Tumors of the Female Reproductive Tract Adrenal Tumors Hamster Kidney Tumors Other Tissues8 Progesterone Blood Formed Elements Plasma Oviduct Entry into the Cell Intracellular Distribution Cytoplasmic Binding Nuclear Binding Uterus Entry into the Cell Compounds Present within the Cell Intracellular Distribution Rat Guinea Pig Rabbit Human Specificity Other Tissues Brain and Pituitary Gland Mammary Gland Corpus Luteum Decidua9 Relationship of Binding to Biological Activity Introduction Evidence that the Steroid-Receptor Interaction is Related to the Biological Activity of the Steroid Estrogens Progestins Androgens Glucocorticoids Mineralocorticoids Physiological Aspects of Steroid-Receptor Interaction Introduction Uterus Oviduct Brain and Anterior Pituitary Gland Tumors Na+-K+ Transport Mammary Gland Accessory Sex Glands in the Male The Molecular Aspects of Steroid-Receptor Interaction Introduction The Relative Importance of the Components of the Steroid-Receptor Complex A Comparison of Steroid Receptors with the Regulatory Proteins in Microorganisms Current Concepts of the Structure and Function of Chromatin The Interaction of Steroid-Binding Proteins with Chromatin The Specificity of Hormonal Responses The Molecular Events Stimulated by Receptor-Nucleus Interaction The Possible Role of Cyclic AMP in Steroid Hormone Action Effects of Hormones Achieved without a Necessary Dependence on Nuclear Processes and High Affinity Binding10 Clinical and Immunological Aspects of Steroid-Binding Terminology Plasma Proteins Tissue Proteins Steroid AntibodiesAppendix 1 Chemical and Trivial Names of SteroidsAppendix 2 Structure of Synthetic CompoundsAppendix 3 An Up-to-Date Summary of Current Literature