Anabolic-Androgenic Steroids

743 Pages·1976·39.23 MB·English

by  C. D. Kochakian (auth.)

Handbuch der experimentellen
Pharmakologie
Vol. 43
Heffter-Heubner New Series
Handbook of Experimental
Pharmacology
H erausgeber Editorial Board
G. V. R. Born, Cambridge· O. Eichler, Heidelberg
A. Farah, Rensselaer, NY . H. Herken, Berlin
A. D. Weleh, Memphis, TN
Beirat Advisory Board
E. J. Ariens . Z. M. Bacq . P. Calabresi . S. Ebashi . E. G. Erdos
V. Erspamer . U. S. von Euler· w. S. Feldberg· G. B. Koelle· O. Krayer
T. A. Loomis . H.Raskova· M.Rocha e Silva· F.Sakai· J.R. Vane
P.G. Waser· W. Wilbrandt
Anabolic-Androgenic
Steroids
Contributors
N.Arimasa· A.Arnold· D.L.Bennett . A.L.Beyler
W. A.Daniel . J. A. Friedland· G. S. Gordan
C. W. Gurney· R. Hilf . A. B. Houssay . C. D. Kochakian
H.Kopera· R.L.Landau· I. Lewin . T.W.Perry
G.O.Potts· A.J.Ryan· H.Spencer
Editor
Charles D. Kochakian
With 38 Figures
Springer-Verlag Berlin Heidelberg New York 1976
CHARLES D. KOCHAKIAN, Ph. D., Director and Professor, Experimental Endocrinol
ogy, The University of Alabama in Birmingham, Medical Center, 1919 Seventh
Avenue South, Birmingham, AL 35294jUSA
ISBN-13: 978-3-642-66355-0 e-ISBN-13: 978-3-642-66353-6
DOl: 10.1007/978-3-642-66353-6
Library of Congress Cataloging in Publication Data. Main entry under title: Anabolic-androgenic steroids. (Handbook of experimental
pharmacology: New series; v. 43). Includes bibliographies and indexes. 1. Androgens. 2. Anabolic steroids. 3. Androgens-Therapeutic use.
4. Anabolic steroids-Therapeutic use. I. Arimasa, N. II. Kochakian, Charles D., 1908-'- III. Series: Handbuch der experirnentellen
Pharmakologie: New series; v. 43. QP905.H3 vol. 43 [QP572.A5] 615'.1'08s [599'.01'927]76-12989
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Sof'tcover reprint of the hardcover I st edition 1976
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Preface
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.
The editor has chosen to write most of the chapters related to the basic aspects
of the action of the anabolic-androgenic steroids and for the clinical areas has
selected contributors who have been active not only in research but in the clinical
application of these steroids. Since the material for these chapters could readily
overlap with consequent duplication and also possible serious omissions, a con
ference of these contributors was held on January 27, 1975. A detailed review was
presented by each contributor with active informal discussion. The conference
proved of great value. Changes were made and hopefully overlap and omissions
have been minimized.
I would like to thank the many contributors for their enthusiastic interest and
cooperation. I wish to especially thank Richard Landau for his many constructive
suggestions and Allan Kenyon for his interest and suggestions. Finally, I wish to
express my appreciation to my secretary, Frances Youngblood, for her dedicated
assistance in the many details of editing such a volume and the extensive typing and
literature search required in the preparation of my chapters. To my wife, lowe my
special gratitude for her continuous support and laboratory assistance during the
initiation of the renotrophic-androgenic and enzyme studies.
Autumn, 1976 CHARLES D. KOCHAKIAN
Table of Contents
I. Historical Review of Anabolic-Androgenic Steroids. C. D. KOCHAKIAN
References 3
II. Metabolic Effects
A. Metabolic Effects of Anabolic-Androgenic Steroids in Experimental Animals.
C. D. KOCHAKIAN. With 3 Figures
I. Introduction. . . . . . . . . . . 5
A. Early Studies . . . . . . . . . 5
B. Establishment of Anabolic Action. 5
1. Dog. . . . . . . . . . . . 5
2. Rat . . . . . . . . . . . . 7
II. Comparison of Protein Anabolic Activity of Natural and Synthetic
Steroids. . . . . . . 9
A. Assay Procedure in Rat . . . . 9
B. Comparison of Steroids. . . . 12
1. Subcutaneous Administration 13
2. Oral Administration . . . . 13
III. Effect of Castration on Protein and Energy Metabolism . 13
A. Dog. . . 13
B. Rat. . . . 14
C. Guinea Pig 15
D.Fowl. . . 15
IV. Effect of Endocrine Status on Anabolic Activity of Steroids. 15
A. Testis. . 15
1. Dog. . 15
2. Rat . . 15
3. Rabbit. 16
B. Ovary . 17
1. Rat . . 17
2. Dog. . 17
3. Monkey 18
C. Pituitary 18
1. Dog. 18
2. Rat . 18
D. Thyroid. 20
Rat . . 20
VIII Table of Contents
E. Adrenals 21
Rat . . 21
F. Pancreas 22
1. Dog. 22
2~. ~
V. Effect of Nutritive State on Anabolic Activity of Steroids. 26
A. Rat . . . . . . . . 26
1. Quantity of Protein . . 26
2. Quality of Protein . . . 27
3. Depletion and Repletion 27
B. Guinea Pig . . . . . . 29
C. Dog. . . . . . . . . 29
VI. Kinetics of Protein Synthesis 29
[15NJ-Glycine Studies. . . 29
VII. Nitrogen Constituents of Urine and Blood 30
A. NPN, Urea, Amino-N and Protein 30
1. Urine . . . . . 30
2. Blood . . . . . 30
B. Creatine-Creatinine 32
1. Dog. . 32
2. Rat . . 32
3. Monkey 33
4. Rabbit . 34
5. Guinea Pig 34
C. Coproporphyrin . 35
VIII. Electrolytes and Water. 35
A. Dog. 35
B. Rat . 36
C. Mouse 36
D. Rabbit 36
IX. Energy Metabolism 37
A. Dog. 37
B. Rat . 37
X. Summary 37
References. . . 39
B. The Metabolic Effects of Anabolic Steroids in Man. R. L. LANDAU.
With 10 Figures
I. The Anabolic Effect of Testosterone. 45
II. Salt-Retaining Action of Testosterone 54
III. Anabolic Effects of Estrogen . . .. 54
IV. Effect of Estrogen on Salt Metabolism. 56
V. The Use of Androgen in Debilitated States. 57
VI. Effects of Androgens on Carbohydrate and Fat Metabolism. 63
VII. Synthetic Testosterone Analogues 64
VIII. Conclusions 67
References. . . . . . . . . . . . . 68
Table of Contents IX
III. Sites of Tissue Formation
A. Body and Organ Weights and Composition. C. D. KOCHAKIAN. With 13 Figures
I. Introduction . 73
II. Body Weight and Composition 73
A. Effect of Castration. 73
1. Rat 73
2. Mouse. 74
3. Guinea Pig 75
4. Hamster. 76
B. Steroid Administration 76
1. Rat 76
2. Mouse. 86
3. Guinea Pig 88
4. Hamster 89
5. Monkey 89
6. Rabbit. 89
III. Muscle 90
Introduction . 90
1. Guinea Pig . 90
2. Rat 96
3. Mice. 102
4. Rabbit. 103
5. Other Species . 103
IV. Urinary Bladder 104
A. Mouse 104
B. Rat 104
C. Dog 105
V. Internal Organs. 105
A. Kidney. 106
1. Rat 106
2. Mouse. 112
3. Guinea Pig 120
4. Hamster 120
5. Rabbit. 120
6. Dog. 121
7. Human. 121
8. Compensatory Renal Hypertrophy. 121
B. Liver. 123
1. Rat 123
2. Mouse. 126
3. Guinea Pig 127
4. Hamster 127
5. Dog. 128
C. Heart. · 128
1. Rat · 128
2. Mouse. · 130
x Table of Contents
D. Thymus and Spleen. 130
1. Rat . . . 130
2. Mouse .... 132
3. Guinea Pig. . 134
E. Lacrimal Glands. 134
1. Rat . . 134
2. Mouse ... . 136
3. Rabbit ... . 140
F. Gastrointestinal Tract. 140
1. Rat . . .... . 140
2. Mouse ..... . 142
VI. Summary and Conclusions . 143
References. . . . . . . . . . . 143
B. Effect of Anabolic-Androgenic Steroids on the Skin, Including Hair and Sebaceous
Glands. A. B. HOUSSAY. With 2 Figures
I. Effects upon the General Properties of the Skin. 155
A. Mechanical Properties . . 155
B. Collagen Content . . . . 156
C. Skin Mucopolysaccharides. 156
D. Anabolic Effects . . . . . 158
II. Metabolism of Androgens by the Skin 159
III. Effects of Androgens on Hair Growth in Experimental Animals. 161
A. Hair Growth in Waves in Rats and Mice. 161
B. Effects of Castration . . . 162
C. Effect of Steroid Hormones . . . . . . . 163
D. Effects in Other Mammals. . . . . . . . 164
IV. Metabolism of Androgens by the Rat Skin in Relation to the Hair Cycles 165
V. Effects of Androgens upon Hair Growth in Man. 165
A. Effects on Scalp Hair . . . . . . 166
B. Effects on Axillary and Pubic Hair . . . . . . 167
C. Effects on Masculine Hair. . . . . . . . . . 168
VI. Metabolism of Androgens by Isolated Human Hair Follicles. 170
VII. Effects of Androgens upon Sebaceous Glands in Experimental Animals 170
A. Effect on Sebaceous Glands of Rats 170
B. Effects on Hamster Flank Organ. . . . . . . . 172
C. Effects on Rat Preputial Glands. . . . . . . . 173
D. Effects on Sebaceous Glands of Other Mammals. 173
VIII. Effects of Androgens in Human Sebaceous Glands. . 174
Androgens and Acne. . . . . . . . . . . . . . . 175
IX. Metabolism of Androgens in the Sebaceous Glands . 176
References. . . . . . . . . . . . . . . . . . . . . . 177
C. Anabolic-Androgenic Steroids and Experimental Mammary Tumors. R. HILF
I. Introduction. . . . . . . . . . . . . . . . . 191
II. Effect of Androgens on Mouse Mammary Tumors 192
Table of Contents XI
III. Androgens and Rat Mammary Tumors. 195
A. Transplanted Mammary Tumors in Rats. · 196
1. Fibroadenomas. . . . . . . . . . · 196
2. Carcinomas. . . . . . . . . ... · 197
B. Carcinogen-Induced Mammary Tumors in Rats. .201
IV. Mammary Tumors in Vitro. . . . . . . . . . . .204
V. Effects of Androgens on Other Experimental Tumor Systems. .205
VI. Conclusions .206
References. . . . . . . .207
IV. Mechanism of Action
A. Regulation of Protein Synthesis by Anabolic-Androgenic Steroids.
C. D. KOCHAKIAN
I. Introduction . 211
II. Studies in Vivo 211
A. Mouse .. 211
B. Rate ... 212
1. 4C] Amino Acids · 212
2. [14C]-Formate . . · 213
3. Anticatabolic Effects . · 214
C. Guinea Pig . . . . · 214
D. Rabbit ..... . · 215
III. Studies in Vivo/in Vitro · 216
A. Rat ...... . · 216
1. Liver and Kidney Slices. · 216
2. Kidney Cell-free System · 216
3. Heart Slices. . . . . . · 217
4. Skeletal Muscles. . . . · 217
5. Perineal Muscle ("Levator Ani") Slices · 219
B. Mouse ............ . · 219
1. Kidney, Liver, and Muscle Slices. · 219
2. Kidney Homogenate . .' .220
3. Kidney Cell-free Systems .220
C. Guinea Pig . . . . . . . .223
1. Kidney Cell-free System. · 223
2. Muscle Cell-free System. .224
IV. Studies in Vitro. . . .224
A. Liver Slices . . . .224
B. Perineal Muscles. .225
"Levator Ani" . .225
V. Summary .225
References. . . . . . . .226
B. Regulation of Nucleic Acid Synthesis by Anabolic-Androgenic Steroids.
C. D. KOCHAKIAN
I. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . 229
XII Table of Contents
II. Mouse ...... . .229
A. Kidney .... . .229
1. Total Changes. .229
2. Subcellular Changes · 231
3. Biosynthesis · 232
B. Liver. . . . . · 236
C. Thymus .... · 236
D. Perineal Muscle · 236
"Levator Ani" . · 236
III. Rat. . . . . . . · 236
A. Liver and Kidney. · 236
B. Muscle .. · 239
1. Skeletal · 239
2. Perineal .240
IV. Guinea Pig. . .242
Skeletal Muscle. .242
V. Rabbit. . · 243
Heart. . · 243
VI. Summary · 243
References. . . .244
C. Regulation of Tissue Enzymes. C. D. KOCHAKIAN
I. Introduction. . . . . 247
II. Kidney . . . . . . . . . . . . . . . . . 247
A. Amino Acid-Related . . . . . . . . . . 247
1. Transaminases and Glutamic Acid Dehydrogenase. 247
2. D-Amino Acid Oxidase. 248
3. Arginase. . . . . 249
4. Transcarbamylases 252
5. Amidotransferases . 253
6. Histamine Methyltransferase 253
7. Histidine Decarboxylase 254
8. Ornithine Decarboxylase 254
9. Cathepsin . . . . 254
10. Acetylating Enzyme 255
11. Aminopeptidase. 255
B. Hydrolases . . 255
1. Phosphatases . 255
2. Esterases. . . 259
3. Ribonucleases. 260
4. p-Glucuronidase. 261
5. Glycosidases . . 263
C. Oxidative and Glycolytic Enzymes . 264
D. p-Hydroxybutyrate Dehydrogenase. 264
E. Alcohol Dehydrogenase. 265
III. Liver . . . . . . . . 266
A. Amino Acid-Related . . 266