The Adrenocortical Hormones

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Table of Contents

Professor Helen Wendler Deane Markham, 1917–1966.- 9: Control of Aldosterone Secretion.- Methods Used to Measure the Rate of Aldosterone Secretion.- A. Adrenocortical Histology.- B. Sodium and Potassium Excretion.- C. Direct Measurement of Aldosterone in Body Fluids.- I. Bioassay.- II. Chemical Identification.- III. Isotope Derivative and Dilution Methods.- IV. Special Problems in the Measurement of Aldosterone in Urine.- V. Special Problems in the Measurement of Aldosterone in Adrenal-Venous Blood.- VI. Measurement of Aldosterone in Peripheral Blood.- D. Determination of Secretion Rate by Dilution of Isotopic Aldosterone.- Effccts of Changes in Plasma Electrolyte Levels on Aldosterone Secretion.- ACTH and the Control of Aldosterone Secretion.- A. Effect of Hypophysectomy on Adrenal Histology.- B. Effcct of Hypophysectomy on Aldosterone Secretion.- C. Effect of ACTH on Aldosterone Secretion.- D. Possible Indirect Effects of ACTH on Aldosterone Secretion.- E. Control of ACTH Secretion.- The Renin-Angiotensin System and the Control of Aldosterone Secretion.- A. The Effect of Renin and Angiotensin II on Aldosterone Secretion.- I. Mechanism of Action of Angiotensin II on the Adrenal Cortex.- II. Effects of Endogenous Renin.- B. Other Effects of Angiotensin II.- I. Variations in Pressor Response.- II. Effects on the Kidney.- C. Metabolism of Angiotensin II.- D. Renin.- E. Comparative Physiology of the Renin-Angiotensin System.- F. The Juxtaglomerular Apparatus as the Source of Renin.- G. Stimulation of Renin Secretion.- I. Methods for Measuring Renin and Angiotensin II in Body Fluids.- II. Other Indices of Renin Secretion.- III. Stimuli Affecting Renin Secretion and Their Mode of Action.- 1. Role of the Pressure Gradient Across the JG Cells.- 2. Chronic Renal Hypertension.- 3. Effects of Changes in Pulse Pressure.- 4. Effect of Renal Arteriolar Constriction.- 5. Effects of Other Stimuli.- 6. Other Theories of the Control of Renin Secretion.- Interactions Between ACTH and Angiotensin II.- A. ACTH Deficiency.- I. Acute.- II. Chronic.- B. ACTH Excess and Compensatory Hypertrophy.- C. Angiotensin II Deficiency.- D. Angiotensin II Excess.- I. Acute.- II. Chronic.- E. ACTH and Renin Secretion.- Possible Neural Regulatory Mechanisms.- A. Role of the Anteroventral Hypothalamus.- B. Role of the Posterior Diencephalon and Neighboring Structures.- Effect of Growth Hormone on Aldosterone Secretion.- Effects of Other Hormones on Aldosterone Secretion.- Stimuli Affecting Aldosterone Secretion and Probable Pathways through which they Exert their Effects.- A. Basal Secretion and Diurnal Rhythm.- B. Stimuli that Increase both Aldosterone and Glucocorticoid Secretion.- C. Stimuli that Increase Aldosterone Secretion Selectively.- I. Relation to Plasma Sodium and Potassium Levels.- II. The Role of the Renin-Angiotensin System.- 1. Cardiovascular Manipulations.- 2. Low-salt Diet and Sodium Depletion.- 3. Secondary Hyperaldosteronism.- 4. Other Stimuli.- D. Stimuli that Decrease Aldosterone Secretion.- E. Negative Feedback Control of Aldosterone Secretion.- Effects of Variations in Aldosterone Metabolism on Aldosterone Secretion.- Relation between Aldosterone Secretion and the Autonomic Nervous System.- Other Mechanisms Regulating Sodium and Potassium Excretion.- A. “Escape” Mechanism.- B. Diuretic Response to Expansion of Extracellular Fluid Volume.- Conclusions.- Appendix: Chemical Names for Substances Mentioned in Text.- Literature.- 10: Manifestations of Hypersecretion of Adrenal Sex Steroids in Man..- The Human Fetus.- A. Embryology.- I. Genetic Sex.- II. Adrenal Cortex.- 1. The Fetal Adrenal Gland and Its Relationship to Congenital Adrenal Hyperplasia.- 2. Steroid Biosynthesis in the Fetal Adrenal Gland.- III. The Gonads.- 1. The Undifferentiated Stage.- 2. The Testis.- 3. The Ovary.- IV. The External Genitalia.- 1. Indifferent Stage.- 2. Male.- 3. Female.- V. Summary of Embryology.- Pseudohermaphroditism.- A. Pseudohermaphroditism not of Adrenal Origin.- I. Maternal Tumor.- II. Medication During Pregnancy.- III. Association with Other Congenital Anomalies.- IV. Isolated Anomaly of Unknown Etiology.- B. Pseudohermaphroditism Associated with Congenital Adrenal Hyperplasia.- Congenital Adrenal Hyperplasia.- A. Introduction.- I. Heredity.- II. General Pathogenesis.- III. Postulated Normal Steroid Biosynthetic Pathways.- B. Congenital Adrenal Hyperplasia with Virilism.- I. Clinical Description.- II. The Postulated Enzymatic Defect.- III. Production of Adrenal Androgens and Estrogens.- IV. Steroid Content and Steroid Transformations in Adrenal Glands.- C. Congenital Adrenal Hyperplasia Complicated by Electrolyte Imbalance.- I. Common Form.- 1. Clinical Description.- 2. Pathogenesis.- a) The Postulated Enzymatic Defect.- b) Possible Salt-Excreting Factor.- c) Aldosterone Production.- d) Consideration of the Etiology of Electrolyte Imbalance in Congenital Adrenal Hyperplasia.- II. Atypical Form of Congenital Adrenal Hyperplasia.- 1. Clinical Description.- 2. Pathogenesis.- 3. Possible Additional Cases.- D. Congenital Adrenal Hyperplasia Complicated by Hypertension.- I. Clinical Description.- II. Pathogenesis.- E. Congenital Adrenal Hyperplasia Complicated by Fever.- I. Clinical Description.- II. Pathogenesis.- F. Congenital Adrenal Hyperplasia Complicated by Hypoglycemia.- I. Clinical Description.- II. Pathogenesis.- G. Involvement of Other Endocrine Glands.- I. The Pituitary.- II. Testes.- III. Ovaries.- H. Etiology of Congenital Adrenal Hyperplasia.- Acquired Syndromes.- A. Adrenal Hyperplasia.- I. Associated with Masculinization.- II. Associated with Feminization.- III. Associated with Excessive Glucocorticoid and Sex Hormone Production.- 1. Introduction.- 2. Clinical Manifestations of Hypercortisolemia and Excessive Sex Hormone Production in Patients with Cushing’s Syndrome.- 3. Excretion of 17-Ketosteroids in Relation to Adrenal Pathology.- 4. Studies of Androgens and Estrogens in Patients with Hypercortisolemia Associated with Adrenal Hyperplasia.- B. Adrenal Tumors.- I. So-Called Non-Functioning Adrenal Tumors.- II. Benign Adrenal Tumors Associated with Abnormal Endocrinological Manifestations.- 1. Adrenal Adenomas Associated with Androgenic Manifestations.- 2. Benign Adrenal Tumors Associated with Estrogenic Manifestations.- III. Excessive Sex Hormone Secretion in Patients with Hypercortisolemia Associated with Adrenal Adenoma.- IV. Malignant Adrenal Tumors.- 1. Adrenocortical Carcinoma Associated with Virilization Only or with Additional Manifestations of Cushing’s Syndrome.- 2. Malignant Adrenal Tumors Associated with Feminization.- a) Clinical Description.- b) Steroid Determinations in Patients with Feminization Associated with Adrenal Tumors.- 3. Excessive Production of Estrogens in Adrenocortical Carcinoma Associated with Cushing’s Syndrome.- C. Clinical Tests of Some Value in Characterizing the Nature of Adrenocortical Pathology.- I. Acquired Adrenal Hyperplasia.- II. Benign Adrenal Tumors.- III. Malignant Adrenal Tumors.- Testosterone Determinations in Biological Fluids.- Literature.- 11: Control of Corticotrophin Secretion.- The Assessment of Hypothalamo-Pituitary-Adrenocortical Activity.- Regulation of Pituitary Adrenocorticotrophic Activity.- A. The Role of the Sympathetic Nervous System.- B. The Role of the Central Nervous System.- C. The Role of Corticosteroids.- D. Locus of Action of Corticosteroids in Feedback Mechanism.- E. The Role of Circulating Corticotrophin.- Conclusion.- Literature.- 12: On the Pharmacologic Actions of 21-Carbon Hormonal Steroids (“Glucocorticoids”) of the Adrenal Cortex in Mammals.- General Considerations.- Mechanism of Action of Glucocorticoids.- Action of Glucocorticoids on Enzymes and Lysosomes.- A. Glucocorticoids and Enzyme Activity.- I. Introduction.- II. Enzymes Responsive to Glucocorticoids.- 1. Enzymes of Carbohydrate Metabolism.- a) Glucose-6-phosphatase.- b) Fructose-1,6-diphosphatase.- c) Other Enzymes of Carbohydrate Metabolism.- 2. Amino Acid Metabolism.- a) Trytophan Pyrrolase.- b) Other Enzymes of Amino Acid Metabolism.- 3. Miscellaneous Enzymes.- III. Mechanism of Glucocorticoid Action on Enzyme Systems.- IV. Significance of Glucocorticoid Actions on Enzyme Systems.- B. Glucocorticoids and Lysosomes.- I. Introduction.- II. Glucocorticoid Effects on Lysosomes.- 1. Protection Against the Effects of Ultraviolet Irradiation.- 2. Protection Against Toxic Effects of Vitamin A.- 3. Protection Against the Effects of Bacterial Toxins.- III. Mechanism of Glucocorticoid Action on Lysosomes.- 1. Structure-Activity Relationships.- 2. Proposed Mechanisms of Action.- IV. Significance of Glucocortieoid-Lysosomal Interactions.- 1. Tissue Damage and Repair.- 2. Fever and Disease State.- V. Summary.- Action of Glucocorticoids on Cells, Tissues, Organs and Systems.- A. Nervous System.- I. Peripheral Nerve.- II. Brain.- 1. Anatomy.- 2. Physiology.- 3. Metabolism.- 4. Cerebral Edema.- B. Eye.- C. Connective Tissue.- I. Fibroblasts.- II. Mast Cells.- D. Skeletal Muscle.- E. Bone, Cartilage and Calcium Metabolism.- F. Skin.- G. Blood.- I. Hematopoiesis and Red Blood Cells.- II. Coagulation.- III. Eosinophils.- IV. Polymorphonuclear Leukocytes.- V. Basophils.- VI. Lymphocytes.- H. Gastrointestinal Tract.- I. Stomach.- 1. Clinical Data.- 2. Experimental Data.- II. Pancreas.- III. Liver.- J. Cardiovascular System.- I. Heart.- II. Blood Vessels.- K. Lung.- Pharmacologic Actions of Glucocorticoids in Man.- A. Naturally Occurring and Pharmacologically Induced Hypercortisolism.- B. Effects on Intermediary Metabolism.- I. Protein Metabolism.- 1. Introduction – Nitrogen Balance, Amino Acids, and Gluconeogenesis.- 2. Plasma Proteins.- 3. Myopathy.- 4. Skin.- II. Carbohydrate Metabolism.- 1. Carbohydrate Tolerance.- 2. Gluconeogenesis.- 3. Renal Effects and Glucose.- 2. Insulin and Pancreatic Islet Cell Reserve.- 5. Glucose Utilization.- 6. Unique Effects of Glucocorticoids on Carbohydrate Metabolism.- III. Lipid Metabolism.- 1. General Comments.- 2. Nodular Panniculitis.- C. Effects on Blood Pressure.- D. Effects on Organs and Systems.- I. Central Nervous System.- 1. Introduction.- 2. Generally Observed Organic Effects.- 3. Electroencephalography.- 4. Psychic Effects.- II. Eye.- 1. Introduction.- 2. Intraocular Pressure-“Corticosteroid Glaucoma”.- 3. Cataract Formation.- III. Bone.- 1. Osteoporosis.- a) Histology.- b) Radiography.- 2. Pathological Fractures.- 3. Joint Degeneration.- 4. Calcium Metabolism.- IV. Kidney.- 1. Renal Function and Water and Electrolyte Balance.- a) Glomerular Filtration and Tubular Functions; Mechanisms.- b) Diurnal Rhythms and Metabolism of Sodium and Potassium.- c) Summary of Glucocorticoid Effects on Electrolytess.- 2. Hypokalemic Alkalosis.- V. Endocrine Organs and Functions.- 1. Thyroid.- 2. Ovary.- a) Amenorrhea.- b) Pregnancy and the Fetal Adrenal Gland.- c) Ovarian Pathology.- 3. Pituitary-Adrenal Axis.- 4. Growth.- a) Linear Growth.- b) Antagonism of Growth Hormone.- 5. Adrenocortical Steroids and Parathyroid Hormone.- Literature.

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