Anabolic-Androgenic Steroids

ISBN-13: 9783642663550 / Angielski / Miękka / 2011 / 726 str.

N. Arimasa;A. Arnold;D.L. Bennett

Opis

This volume was planned to provide a comprehensive survey of the role of the anabolic-androgenic steroids in the vital economy exclusive of the androgenic (sexual) functions. It seemed appropriate to bring together all of this information in an organized fashion in one volume at this time not only to serve as a source of information but also to indicate and suggest areas that need further exploration. The anabolic action of the steroid hormones has gone through a period of great activity in both basic and clinical research. A complete understanding of the manifold anabolic effects still remains to be elucidated and the art of clinical application is only gradually becoming apparent. This volume should be useful not only to the experienced investigator in both basic and clinical research but also for the novice. Furthermore, it should serve as a source of information for the careful use of these steroids in certain metabolic diseases. These steroids have had wide clinical application with variable results. In many instances further careful exploration is suggested. Other instances have demonstrated varying degrees of usefulness.

Spis treści

I. Historical Review of Anabolic-Androgenic Steroids..- References.- II. Metabolic Effects.- A. Metabolic Effects of Anabolic-Androgenic Steroids in Experimental Animals..- I. Introduction.- A. Early Studies.- B. Establishment of Anabolic Action.- 1. Dog.- 2. Rat.- II. Comparison of Protein Anabolic Activity of Natural and Synthetic Steroids.- A. Assay Procedure in Rat.- B. Comparison of Steroids.- 1. Subcutaneous Administration.- 2. Oral Administration.- III. Effect of Castration on Protein and Energy Metabolism.- A. Dog.- B. Rat.- C. Guinea Pig.- D. Fowl.- IV. Effect of Endocrine Status on Anabolic Activity of Steroids.- A. Testis.- 1. Dog.- 2. Rat.- 3. Rabbit.- B. Ovary.- 1. Rat.- 2. Dog.- 3. Monkey.- C. Pituitary.- 1. Dog.- 2. Rat.- D. Thyroid.- Rat.- E. Adrenals.- Rat.- F. Pancreas.- 1. Dog.- 2. Rat.- V. Effect of Nutritive State on Anabolic Activity of Steroids.- A. Rat.- 1. Quantity of Protein.- 2. Quality of Protein.- 3. Depletion and Repletion.- B. Guinea Pig.- C. Dog.- VI. Kinetics of Protein Synthesis.- [15N]-Glycine Studies.- VII. Nitrogen Constituents of Urine and Blood.- A. NPN, Urea, Amino-N and Protein.- 1. Urine.- 2. Blood.- B. Creatine-Creatinine.- 1. Dog.- 2. Rat.- 3. Monkey.- 4. Rabbit.- 5. Guinea Pig.- C. Coproporphyrin.- VIII. Electrolytes and Water.- A. Dog.- B. Rat.- C. Mouse.- D. Rabbit.- IX. Energy Metabolism.- A. Dog.- B. Rat.- X. Summary.- References.- B. The Metabolic Effects of Anabolic Steroids in Man..- I. The Anabolic Effect of Testosterone.- II. Salt-Retaining Action of Testosterone.- III. Anabolic Effects of Estrogen.- IV. Effect of Estrogen on Salt Metabolism.- V. The Use of Androgen in Debilitated States.- VI. Effects of Androgens on Carbohydrate and Fat Metabolism.- VII. Synthetic Testosterone Analogues.- VIII. Conclusions.- References.- III. Sites of Tissue Formation.- A. Body and Organ Weights and Composition..- I. Introduction.- II. Body Weight and Composition.- A. Effect of Castration.- 1. Rat.- 2. Mouse.- 3. Guinea Pig.- 4. Hamster.- B. Steroid Administration.- 1. Rat.- 2. Mouse.- 3. Guinea Pig.- 4. Hamster.- 5. Monkey.- 6. Rabbit.- III. Muscle.- 1. Guinea Pig.- 2. Rat.- 3. Mice.- 4. Rabbit.- 5. Other Species.- IV. Urinary Bladder.- A. Mouse.- B. Rat.- C. Dog.- V. Internal Organs.- A. Kidney.- 1. Rat.- 2. Mouse.- 3. Guinea Pig.- 4. Hamster.- 5. Rabbit.- 6. Dog.- 7. Human.- 8. Compensatory Renal Hypertrophy.- B. Liver.- 1. Rat.- 2. Mouse.- 3. Guinea Pig.- 4. Hamster.- 5. Dog.- C. Heart.- 1. Rat.- 2. Mouse.- D. Thymus and Spleen.- 1. Rat.- 2. Mouse.- 3. Guinea Pig.- E. Lacrimal Glands.- 1. Rat.- 2. Mouse.- 3. Rabbit.- F. Gastrointestinal Tract.- 1. Rat.- 2. Mouse.- VI. Summary and Conclusions.- References.- B. Effect of Anabolic-Androgenic Steroids on the Skin, Including Hair and Sebaceous Glands..- I. Effects upon the General Properties of the Skin.- A. Mechanical Properties.- B. Collagen Content.- C. Skin Mucopolysaccharides.- D. Anabolic Effects.- II. Metabolism of Androgens by the Skin.- III. Effects of Androgens on Hair Growth in Experimental Animals.- A. Hair Growth in Waves in Rats and Mice.- B. Effects of Castration.- C. Effect of Steroid Hormones.- D. Effects in Other Mammals.- IV. Metabolism of Androgens by the Rat Skin in Relation to the Hair Cycles.- V. Effects of Androgens upon Hair Growth in Man.- A. Effects on Scalp Hair.- B. Effects on Axillary and Pubic Hair.- C. Effects on Masculine Hair.- VI. Metabolism of Androgens by Isolated Human Hair Follicles.- VII. Effects of Androgens upon Sebaceous Glands in Experimental Animals.- A. Effect on Sebaceous Glands of Rats.- B. Effects on Hamster Flank Organ.- C. Effects on Rat Preputial Glands.- D. Effects on Sebaceous Glands of Other Mammals.- VIII. Effects of Androgens in Human Sebaceous Glands.- Androgens and Acne.- IX. Metabolism of Androgens in the Sebaceous Glands.- References.- C. Anabolic-Androgenic Steroids and Experimental Mammary Tumors..- I. Introduction.- II. Effect of Androgens on Mouse Mammary Tumors.- III. Androgens and Rat Mammary Tumors.- A. Transplanted Mammary Tumors in Rats.- 1. Fibroadenomas.- 2. Carcinomas.- B. Carcinogen-Induced Mammary Tumors in Rats.- IV. Mammary Tumors in Vitro.- V. Effects of Androgens on Other Experimental Tumor Systems.- VI. Conclusions.- References.- IV. Mechanism of Action.- A. Regulation of Protein Synthesis by Anabolic-Androgenic Steroids..- I. Introduction.- II. Studies in Vivo.- A. Mouse.- B. Rat.- 1. [14C] Amino Acids.- 2. [14C]-Formate.- 3. Anticatabolic Effects.- C. Guinea Pig.- D. Rabbit.- III. Studies in Vivo/in Vitro.- A. Rat.- 1. Liver and Kidney Slices.- 2. Kidney Cell-free System.- 3. Heart Slices.- 4. Skeletal Muscles.- 5. Perineal Muscle (“Levator Ani”) Slices.- B. Mouse.- 1. Kidney, Liver, and Muscle Slices.- 2. Kidney Homogenate.- 3. Kidney Cell-free Systems.- C. Guinea Pig.- 1. Kidney Cell-free System.- 2. Muscle Cell-free System.- IV. Studies in Vitro.- A. Liver Slices.- B. Perineal Muscles.- “Levator Ani”.- V. Summary.- References.- B. Regulation of Nucleic Acid Synthesis by Anabolic-Androgenic Steroids..- I. Introduction.- II. Mouse.- A. Kidney.- 1. Total Changes.- 2. Subcellular Changes.- 3. Biosynthesis.- B. Liver.- C. Thymus.- D. Perineal Muscle.- “Levator Ani”.- III. Rat.- A. Liver and Kidney.- B. Muscle.- 1. Skeletal.- 2. Perineal.- IV. Guinea Pig.- Skeletal Muscle.- V. Rabbit.- Heart.- VI. Summary.- References.- C. Regulation of Tissue Enzymes..- I. Introduction.- II. Kidney.- A. Amino Acid-Related.- 1. Transaminases and Glutamic Acid Dehydrogenase.- 2. D-Amino Acid Oxidase.- 3. Arginase.- 4. Transcarbamylases.- 5. Amidotransferases.- 6. Histamine Methyltransferase.- 7. Histidine Decarboxylase.- 8. Ornithine Decarboxylase.- 9. Cathepsin.- 10. Acetylating Enzyme.- 11. Aminopeptidase.- B. Hydrolases.- 1. Phosphatases.- 2. Esterases.- 3. Ribonucleases.- 4. ?-Glucuronidase.- 5. Glycosidases.- C. Oxidative and Glycolytic Enzymes.- D. ?-Hydroxybutyrate Dehydrogenase.- E. Alcohol Dehydrogenase.- III. Liver.- A. Amino Acid-Related.- 1. Transaminases and Glutamic Acid Dehydrogenase.- 2. D-Amino Acid Oxidase.- 3. Catalase.- 4. Tyrosine Oxidase.- 5. Tryptophan Pyrrolase.- 6. Phenylalanine Hydroxylase.- 7. Monoamine Oxidase.- 8. Arginase.- 9. Arginine Synthetase.- 10. Aspartate- and Ornithine-Transcarbamylases.- 11. Creatine-Synthesizing Enzymes.- 12. Histidase.- 13. Decarboxylases.- B. Hydrolases.- 1. Phosphatases.- 2. Glucose-6-Phosphatase.- 3. Esterases.- C. Folate Enzymes.- D. N-Methylnicotinamide Oxidase.- E. Oxidative and Glycolytic Enzymes.- F. Fatty Acid Dehydrogenase.- IV. Muscle.- A. Amino Acid-Related.- B. Hydrolases.- C. Oxidative and Glycolytic Enzymes.- 1. Rat.- 2. Rabbit.- 3. Guinea Pig.- V. Gastrointestinal Tract.- A. Oxidases, Dehydrogenases, Phosphatases.- 1. Rat.- 2. Mouse.- B. Glycolytic Enzymes.- C. Folate-Metabolizing Enzymes.- D. Amylase.- E. Pepsin.- F. Arginase.- VI. Other Tissues.- VII. Summary.- References.- D. The Metabolism in Vitro of Anabolic-Androgenic Steroids by Mammalian Tissues..- I. Introduction.- II. Sites of Metabolism.- A. Liver.- 1. Rabbit.- 2. Guinea Pig.- 3. Rat.- 4. Human.- 5. Dog.- 6. Mouse.- 7. Chick.- B. Kidney.- 1. Rabbit.- 2. Guinea Pig.- 3. Rat.- 4. Dog.- 5. Monkey.- 6. Mouse.- 7. Human.- C. Blood.- 1. Initial Observations in Several Species.- 2. Rat.- 3. Rabbit.- 4. Human.- D. Skeletal Muscle.- E. Heart.- F. Urinary Bladder.- G. Intestine.- H. Thymus.- I. Bone.- J. Neural Tissues.- 1. Rat.- 2. Monkey.- 3. Human.- 4. Dog.- 5. Guinea Pig.- K. Submaxillary Gland.- L. Oral Mucosa.- III. Subcellular Distribution of C19-Steroid Metabolizing Enzyme Activities in Tissues.- A. 17?-Hydroxy-C19-Steroid Oxidoreductases.- B. 3-Hydroxy-C19-Steroid Oxidoreductases.- C. 5-Reductases(?4-Hydrogenases).- 1. Liver.- 2. Kidney.- IV. Regulation of the Activities of the C19-Steroid Metabolizing Enzymes in Peripheral Tissues.- A. Guinea Pig.- B. Rat.- 1. Sex Differences.- 2. Thyroxine.- 3. Pituitary.- 4. Diabetes.- 5. Drugs.- V. Purification of C19-Steroid Enzymes.- A. 17?-Hydroxy-C19-Steroid Oxidoreductase.- 1. Liver.- 2. Kidney.- 3. Blood.- B. 3?-Hydroxy-C19-Steroid Oxidoreductase.- Rat Liver.- C. 5?-Reductase (?4–5?-Hydrogenase).- Pig.- VI. Summary.- References.- V. Dissociation of the Androgenic and Other Hormonal Activities from the Protein Anabolic Effects of Steroids..- I. Introduction.- II. Experimental Methods for Assessing Anabolic and Androgenic Activities.- A. The Evaluation of Anabolic Properties of Steroids Based on Nitrogen Balance Studies.- 1. Assay for Nitrogen Retention.- 2. Calculations of Relative Anabolic-Androgenic Potencies.- B. The Myotrophic/Androgenic Assay as a Method for Evaluating the Dissociation of Anabolic from Androgenic Activities.- Assay for Myotrophic and Androgenic Activities.- C. The Effect of Anabolic Steroids on Rate of Growth and Efficiency of Feed Utilization.- Method.- D. Fasting Body Weight Loss and Increments in Urinary Excretion of Nitrogen, Phosphorus, and Potassium as Indices of Catabolic Action of Glucocorticoids.- Method.- E. Reversal of Catabolic Action of Glucocorticoids by Anabolic Steroids.- 1. Acute Experiments.- 2. Subacute Experiments.- F. The Anticatabolic Activity of Anabolic Steroids Based on the Suppression of Glucocorticoid Induction of Liver Tryptophan Pyrrolase.- G. Assay of Other Hormonal Activities.- III. Dissociation of Anabolic and Androgenic Activities of Selected Protein Anabolic Steroids.- A. Testosterone-Derived Protein Anabolic Steroids.- 1. Testosterone and 17?-Methyltestosterone.- 2. Chlorotestosterone Acetate.- 3. Fluoxymesterone.- 4. Oxymesterone.- 5. Chloromethyltestosterone.- 6. Thiomesterone.- 7. Methandrostenolone, Methandienone.- 8. Chloro-1-dehydromethyltestosterone.- 9. Bolasterone, Dimethyltestosterone.- B. 19-Nortestosterone-Derived Protein Anabolic Steroids.- 1. 19-Nortestosterone, Nandrolone.- 2. Hydroxy-19-nortestosteronecyclopentylproprionate, Oxabolone.- 3. Chloro-19-nortest osterone Acetate.- 4. Methyl-19-nortestosterone.- 5. Norethandrolone, 17?-Ethyl-9-nortestosterone.- 6. Ethyldienolone.- 7. Norbolethone.- C. Androstane-Derived Protein Anabolic Steroids.- 1. Androstanolone, Stanolone, Androlone, Dihydrotestosterone.- 2. Drostanolone, 2?-Methyldihydrotestosterone, 2?-Methylandrosta-nolone.- 3. Mestanolone, Methylandrostanolone.- 4. Oxymetholone.- D. Heterocyclic Protein Anabolic Steroids.- 1. Stanozolol.- 2. Androisoxazole.- 3. 2?,17-Dimethylandrostan-2-eno[3.2-d]thiazol-17?-ol.- 4. Methyldiazinol.- 5. Dimethazine.- 6. Oxandrolone.- E. Miscellaneous Structures.- 1. Methylandrostenediol.- 2. Methenolone.- 3. Ethylestrenol.- 4. 17-Methyl-3-methylene-l-androsten-17?-ol.- IV. Reversal of the Acute Catabolic Actions of Glucocorticoids by Protein Anabolic Steroids.- A. The Acute Catabolic Actions of Adrenal Glucocorticoids.- B. Reversal of the Catabolic Actions of Glucocorticoids by Protein Anabolic Steroids.- C. The Anticatabolic Activity of Anabolic Steroids Based on the Suppression of Cortisone Acetate Induction of Liver Tryptophan Pyrrolase.- V. Comments and Conclusions.- References.- VI. Animal Husbandry..- I. Sources of Androgens.- II. General Role of Androgens in Animals.- III. Cattle.- IV. Swine.- V. Sheep.- VI. Poultry.- References.- VII. Clinical Applications.- A. Effect of Androgens on Bone, Calcium, and Phosphorus Metabolism..- Effect of Androgens on Mineral Metabolism in Animals and Man.- A. Effect of Androgens in Animals.- 1. Skeletal Growth.- 2. Skeletal Maturation.- 3. Mineralization.- 4. Collagen Formation and Cellular Action of Androgens.- 5. Androgen Effects During Corticosteroid Administration.- 6. Serum Alkaline Phosphatase.- B. Effect of Androgens in Man.- 1. Skeletal Growth and Maturation.- 2. Effect of Androgens on Bone Resorption and Bone Formation.- 3. Effect on Serum Calcium, Phosphorus, and Alkaline Phosphatase.- 4. Effect of Testosterone on Calcium and Phosphorus Balances.- 5. Effect of Other Synthetic Anabolic Agents on Calcium and Phosphorus Balance.- C. Androgen-Estrogen Interaction.- D. Therapeutic Uses of Androgens.- 1. Postmenopausal and Senile Osteoporosis.- 2. Disuse Osteoporosis.- 3. Corticosteroid-Induced Osteoporosis.- 4. Osteogenesis Imperfecta.- References.- B. The Use of Anabolic-Androgenic Steroids in Childhood and Adolescence..- I. Introduction.- II. Growth and Development.- A. Growth.- B. Puberty.- 1. Gonadal Function During Puberty.- 2. The Onset of Puberty.- 3. Pituitary Gonadotropin Function During Puberty.- III. Some Special Considerations in Children and Adolescents.- A. Rate of Growth.- B. Virilization.- C. Liver Problems.- IV. Clinical Uses.- Growth Retardation.- 1. Premature Dystrophic Infants.- 2. Growth Retardation in Older Children.- 3. Hypopituitarism.- V. Problems of Sexual Maturation.- A. Delayed Sexual Maturation.- 1. Klinefelter’s Syndrome.- 2. Gonadal Dysgenesis (Turner’s Syndrome).- B. Precocious Puberty.- C. Blood Diseases.- 1. Aplastic Anemia.- 2. Hemolytic Anemias.- 3. Anemia of Renal Failure.- D. Chronic Wasting Diseases.- 1. Malnutrition and Protein Loss.- 2. With Corticosteroids.- 3. Diabetes Mellitus.- 4. Hyperthyroidism.- 5. Pulmonary Diseases.- 6. Muscular Dystrophy.- E. Miscellaneous Conditions.- 1. Athletics.- 2. Osteogenesis Imperfecta.- 3. Inborn Errors of Metabolism.- 4. Other Conditions.- VI. Conclusions.- References.- C. The Hematologic Effects of Androgens.- I. Introduction.- II. The Effects of Androgens on Erythropoiesis.- A. Effects of Androgenic Steroids on Peripheral Blood Values.- B. Mechanisms of Action of Androgenic Steroids on Red Cell Formation.- III. The Use of Androgens in Treatment of Anemias.- A. Pharmacologic Considerations.- B. Treatment of Hypoplastic Anemias.- C. Treatment of Secondary Anemias.- IV. The Effects of Androgens on Leukopoiesis and the Use of Androgens in Leukopenia.- V. Summary.- References.- D. Cancer in Man..- I. Introduction.- II. Endocrine-Responsive Tumors.- III. Breast Cancer.- A. Attempts to Predict Response.- B. Empirical Response Rates.- C. Evaluation of Efficacy of Treatment.- 1. Established Clinical Variables.- 2. Measurement of Responses.- 3. Other Parameters.- D. Antitumor Efficacy of Steroidal Agents.- 1. Primary Hormonal Therapy.- 2. Secondary Hormonal Therapy.- 3. Combination of Steroids and Cytotoxic Chemotherapy.- E. Hypercalcemia.- 1. Etiology and Pathogenesis.- 2. Treatment of Hypercalcemia.- References.- E. Athletics..- I. Introduction.- II. Clinical and Laboratory Studies.- A. Reports in which no Improvement in Strength or Power is Claimed Following the Administration of Anabolic Steroids.- B. Reports in which Improvement in Strength or Power is Claimed Following Administration of Anabolic Steroids.- C. Discussion of the Results of the Clinical and Laboratory Studies.- III. Control of the Use of Anabolic Steroids.- IV. Ethical Considerations.- V. Summary.- References.- F. Miscellaneous Uses of Anabolic Steroids..- I. Introduction.- II. Rationale for the Clinical Use of Anabolic Steroids.- A. Protein Anabolism.- B. Other Effects.- III. Principles of Therapeutic Investigations.- IV. Clinical Results.- A. Organic Diseases.- 1. Hepatic Disorders.- 2. Renal Disorders.- 3. Cardiac Disorders.- 4. Vascular Disorders and Fibrinolytic Disturbances.- 5. Gastrointestinal Disorders.- 6. Muscular Disorders.- 7. Pulmonary Disorders.- B. Metabolic Diseases.- 1. Diabetes Mellitus.- 2. Hyperlipemias.- 3. Other Metabolic Disorders.- C. Deficiency States and Catabolic Conditions.- 1. Emaciation, Malnutrition.- 2. Surgery.- 3. Convalescence.- D. Other Conditions.- 1. Neurology.- 2. Psychiatry.- 3. Geriatrics.- 4. Immunology.- 5. Catatoxic Effects.- 6. Radiotherapy.- V. Anabolics with Other Drugs.- A. Combination with Cytostatics.- B. Combination with Glucocorticosteroids.- C. Interaction with Other Drugs.- References.- VIII. Appendix.- Author Index.- Addendum.- VII. E. Athletics, A.J. Ryan.