Basic Medical Endocrinology (eBook)

Front Cover 1
Basic Medical Endocrinology 4
Copyright Page 5
Contents 8
List of Figures 14
Preface to the Fourth Edition 28
Preface to the First Edition 30
Preface to the Second Edition 32
Preface to the Third Edition 34
CHAPTER 1 INTRODUCTION 36
Biosynthesis of Hormones 39
Storage and Secretion 43
Hormones in Blood 43
Hormone Degradation 45
Mechanisms of Hormone Action 45
SPECIFICITY 45
CHARACTERISTICS OF RECEPTORS 46
HORMONAL ACTIONS MEDIATED BY INTRACELLULAR RECEPTORS 47
HORMONAL ACTIONS MEDIATED BY SURFACE RECEPTORS 49
The G-protein Coupled Receptors 49
Receptors that Signal through Tyrosine Kinase 54
REGULATION OF HORMONE SECRETION 56
Negative Feedback 56
Positive Feedback 58
Feed Forward 58
MEASUREMENT OF HORMONES 58
Immunoassays 59
Hormone Levels in Blood 61
Suggested Reading 61
CHAPTER 2 PITUITARY GLAND 64
Morphology 64
Physiology of the Anterior Pituitary Gland 66
GLYCOPROTEIN HORMONES 66
GROWTH HORMONE AND PROLACTIN 68
ADRENOCORTICOTROPIN FAMILY 68
DEVELOPMENT OF THE ANTERIOR PITUITARY GLAND 69
REGULATION OF ANTERIOR PITUITARY FUNCTION 70
HYPOPHYSIOTROPIC HORMONES 70
Thyrotropin Releasing Hormone (TRH) 71
Gonadotropin Releasing Hormone 72
Control of GH Secretion 72
Corticotropin Releasing Hormone 72
Dopamine and control of Prolactin Secretion 73
Secretion and Actions of Hypophysiotropic Hormones 73
FEEDBACK CONTROL OF ANTERIOR PITUITARY FUNCTION 73
Physiology of the Posterior Pituitary 74
REGULATION OF POSTERIOR PITUITARY FUNCTION 75
Suggested Reading 76
CHAPTER 3 THYROID GLAND 78
Morphology 78
Thyroid Hormones 79
BIOSYNTHESIS 80
Iodine Trapping 80
Thyroglobulin Synthesis 80
Incorporation of Iodine 81
HORMONE STORAGE 81
SECRETION 81
Control of Thyroid Function 83
EFFECTS OF THYROID-STIMULATING HORMONE 83
EFFECTS OF THE THYROID-STIMULATING IMMUNOGLOBULINS 84
AUTOREGULATION OF THYROID HORMONE SYNTHESIS 84
Thyroid Hormones in Blood 84
Metabolism of Thyroid Hormones 85
Physiological Effects of Thyroid Hormones 87
GROWTH AND MATURATION 87
Skeletal System 87
Central Nervous System 87
AUTONOMIC NERVOUS SYSTEM 87
CARDIOVASCULAR SYSTEM 88
METABOLISM 88
Oxidative Metabolism and Thermogenesis 88
Carbohydrate Metabolism 90
Lipid Metabolism 90
Nitrogen Metabolism 91
Regulation of Thyroid Hormone Secretion 91
Mechanism of Thyroid Hormone Action 92
Suggested Reading 94
CHAPTER 4 ADRENAL GLANDS 96
Morphology 96
Adrenal Cortex 97
ADRENOCORTICAL HORMONES 97
Control of Adrenocortical Hormone Synthesis 101
Adrenal Steroid Hormones in Blood 104
Postsecretory Metabolism of Adrenal Cortical Hormones 104
Physiology of the Mineralocorticoids 106
Effects of Aldosterone on the Kidney 106
Regulation of Aldosterone Secretion 109
PHYSIOLOGY OF THE GLUCOCORTICOIDS 110
Effects on Energy Metabolism 110
Effects on Water Balance 111
Effects on Lung Development 111
Glucocorticoids and Responses to Injury 112
Adrenocortical Function During Stress 116
Mechanism of Action of Glucocorticoids 117
Regulation of Glucocorticoid Secretion 117
Adrenal Medulla 121
BIOSYNTHESIS OF THE MEDULLARY CATECHOLAMINES 121
STORAGE, RELEASE, AND METABOLISM OF MEDULLARY HORMONES 122
PHYSIOLOGICAL ACTIONS OF MEDULLARY HORMONES 123
REGULATION OF ADRENAL MEDULLARY FUNCTION 124
Suggested Reading 124
CHAPTER 5 PRINCIPLES OF HORMONAL INTEGRATION 126
Integration of Hormonal Signals at the Cellular and Molecular Level 126
AUGMENTATION, ANTAGONISM, AND SYNERGY 126
PERMISSIVENESS 128
MAINTAINING SIGNAL FIDELITY 128
Modulation of Responding Systems 128
SENSITIVITY AND CAPACITY 129
SPARE RECEPTORS 131
Hormonal Integration at the Whole Animal Level 132
REDUNDANCY 132
REINFORCEMENT 133
PUSH–PULL MECHANISMS 134
CHAPTER 6 HORMONES OF THE GASTROINTESTINAL TRACT 136
Functional Anatomy of the GI Tract 136
Overview of Digestion and Absorption 139
Hormones of the Gastrointestinal Tract 139
THE GASTRIN/CHOLECYSTOKININ FAMILY 140
Physiological Actions of Gastrin 141
Regulation of Gastrin Secretion 143
Cholecystokinin (CCK) 144
THE SECRETIN/GLUCAGON SUPERFAMILY 147
Secretin 149
GIP (Glucose-dependent Insulinotropic Polypeptide/Gastric Inhibitory Peptide) 151
Glucagon-like Peptides 1 and 2 (GLP-1 and GLP-2) 153
The Pancreatic Polypeptide Family 156
Neurotensin 157
The Motilin/Ghrelin Family 157
Concluding Comments 159
Suggested Reading 162
CHAPTER 7 THE PANCREATIC ISLETS 164
Morphology of the Endocrine Pancreas 164
Glucagon 165
BIOSYNTHESIS, SECRETION, AND METABOLISM 165
PHYSIOLOGICAL ACTIONS OF GLUCAGON 165
Glucose Production 166
Glycogenolysis 166
Gluconeogenesis 167
Lipogenesis and Ketogenesis 168
Ureogenesis 168
REGULATION OF GLUCAGON SECRETION 169
Insulin 169
BIOSYNTHESIS, SECRETION, AND METABOLISM 169
PHYSIOLOGICAL ACTIONS OF INSULIN 170
Effects of Insulin Deficiency 170
Effects on Adipose Tissue 172
Effects on Muscle 173
Effects on Liver 175
MECHANISM OF INSULIN ACTION 178
REGULATION OF INSULIN SECRETION 179
Glucose 179
Other Circulating Metabolites 180
Hormonal and Neural Control 181
Cellular Events 181
Somatostatin 184
Suggested Reading 184
CHAPTER 8 HORMONAL REGULATION OF FUEL METABOLISM 186
General Features of Energy Metabolism 186
BODY FUELS 186
Glucose 186
Glycogen 187
Protein 187
Fat 187
Problems Inherent in the Use of Glucose and Fat as Metabolic Fuels 187
FUEL CONSUMPTION 188
The Glucose Fatty Acid Cycle 188
AMP Activated Kinase (AMPK) 189
Overall Regulation of Blood Glucose Concentration 190
Short-term Regulation 191
Long-term Regulation 191
Integrated Actions of Metabolic Hormones 192
ADIPOSE TISSUE 192
MUSCLE 193
LIVER 193
PANCREATIC ISLETS 194
Regulation of Metabolism During Feeding and Fasting 194
POSTPRANDIAL PERIOD 194
POSTABSORPTIVE PERIOD 195
FASTING 195
Hormonal Interactions During Exercise 197
SHORT-TERM MAXIMAL EFFORT 198
SUSTAINED AEROBIC EXERCISE 198
Long-term Regulation of Fuel Storage 199
ADIPOGENESIS 200
HYPOTHALAMIC CONTROL OF APPETITE AND FOOD INTAKE 201
Peripheral Input to Hypothalamic Feeding and Satiety Neurons 203
ADIPOSITY SIGNALS 203
Leptin 203
Insulin as an Adiposity Signal 205
Adipokines 206
Satiety Signals 207
PERSPECTIVE 208
Suggested Reading 209
CHAPTER 9 REGULATION OF SALT AND WATER BALANCE 210
General Considerations 210
Salt and Water Balance 211
Antidiuretic Hormone (ADH) 213
ANTIDIURETIC EFFECT 214
EFFECTS ON BLOOD PRESSURE 215
REGULATION OF ADH SECRETION 216
Plasma Osmolality 216
Blood Volume 216
Dysfunctional States 217
The Renin-Angiotensin-Aldosterone System 218
ACTIONS OF ANGIOTENSIN II 219
Actions on the Adrenal Cortex 219
Actions on the Kidney 220
Cardiovascular Effects 220
Central Nervous System Effects 220
Regulation of the Renin-Angiotensin-Aldosterone System 221
Atrial Natriuretic Factor (ANF) 221
PHYSIOLOGICAL ACTIONS 223
Cardiovascular Actions 223
Renal Actions 224
Effects on Aldosterone Secretion 224
Other Effects 225
REGULATION OF ANF SECRETION 225
Integrated Compensatory Responses to Changes in Salt and Water Balance 225
HEMORRHAGE 227
Response of the Renin Angiotensin System 227
Response of the ADH System 228
Response of Aldosterone 228
Response of ANF 228
DEHYDRATION 228
SALT LOADING AND DEPLETION 229
Suggested Reading 230
CHAPTER 10 HORMONAL REGULATION OF CALCIUM BALANCE 232
General Features of Calcium Balance 232
DISTRIBUTION OF CALCIUM IN THE BODY 233
CALCIUM BALANCE 233
Intestinal Absorption 234
Bone 234
Kidney 236
Phosphorus Balance 237
Parathyroid Glands and Parathyroid Hormone (PTH) 237
BIOSYNTHESIS, STORAGE, AND SECRETION OF PTH 238
MECHANISMS OF PARATHYROID HORMONE ACTION 239
PHYSIOLOGICAL ACTIONS OF PTH 239
Actions on Bone 239
Actions on Kidney 240
Effects on Intestinal Absorption 242
PTH FRAGMENTS 242
PARATHYROID HORMONE-RELATED PEPTIDE (PTHRP) 242
REGULATION OF PTH SECRETION 243
Calcitonin 244
CELLS OF ORIGIN 244
BIOSYNTHESIS, SECRETION, AND METABOLISM 244
PHYSIOLOGICAL ACTIONS OF CALCITONIN 245
Actions on Bone 245
Actions on Kidney 245
REGULATION OF SECRETION 245
The Vitamin D-Endocrine System 246
SYNTHESIS AND METABOLISM 246
PHYSIOLOGICAL ACTIONS OF 1,25(OH)[sub(2)]D[sub(3)] 246
Actions on Intestine 247
Actions on Bone 248
Actions on Kidney 248
Actions on Parathyroid Glands 248
REGULATION OF 1,25(OH)[sub(2)]D[sub(3)] PRODUCTION 249
Calcium Regulation of Plasma Calcium Concentrations 249
Integrated Actions of Calcitropic Hormones 250
RESPONSE TO A HYPOCALCEMIC CHALLENGE 250
RESPONSE TO A HYPERCALCEMIC CHALLENGE 251
Other Hormones That Influence Calcium Balance 251
Suggested Reading 252
CHAPTER 11 HORMONAL CONTROL OF GROWTH 254
Growth Hormone 254
SYNTHESIS, SECRETION, AND METABOLISM 256
MODE OF ACTION 256
PHYSIOLOGICAL ACTIONS OF GROWTH HORMONE 257
Effects on Skeletal Growth 257
Effects of GH/IGF-I on Body Composition 261
Regulation of GH Secretion 262
Effects of Age 263
Regulators of GH Secretion 264
ACTIONS OF GHRH, SOMATOSTATIN, IGF-I, AND GHRELIN ON THE SOMATOTROPE 266
Thyroid Hormones 266
DEPENDENCE OF GH SYNTHESIS AND SECRETION ON T3 268
IMPORTANCE OF T3 FOR EXPRESSION OF GH ACTIONS 268
Insulin 268
Gonadal Hormones 269
EFFECTS OF ESTROGENS ON EPIPHYSEAL GROWTH PLATES 270
EFFECTS ON GROWTH HORMONE SECRETION AND ACTION 270
EFFECTS OF ANDROGENS 271
Glucocorticoids 272
Suggested Reading 273
CHAPTER 12 HORMONAL CONTROL OF REPRODUCTION IN THE MALE 274
Morphology of the Testes 274
LEYDIG CELLS AND SEMINIFEROUS TUBULES 274
MALE REPRODUCTIVE TRACT 276
Control of Testicular Function 277
LEYDIG CELLS 277
GERMINAL EPITHELIUM 279
Testosterone 280
SECRETION AND METABOLISM 280
MECHANISM OF ACTION 281
EFFECTS ON THE MALE GENITAL TRACT 281
EFFECTS ON SECONDARY SEXUAL CHARACTERISTICS 282
Sexual Differentiation 282
DEVELOPMENT OF INTERNAL REPRODUCTIVE DUCTS AND THEIR DERIVATIVES 283
DEVELOPMENT OF THE EXTERNAL GENITALIA 285
TESTICULAR DESCENT INTO THE SCROTUM 285
POSTNATAL DEVELOPMENT 286
ANOMALIES OF SEXUAL DIFFERENTIATION 286
Regulation of Testicular Function 286
GONADOTROPIN RELEASING HORMONE AND THE HYPOTHALAMIC PULSE GENERATOR 287
NEGATIVE FEEDBACK REGULATORS 289
Inhibin and Testosterone 289
PREPUBERTY 290
PUBERTY 290
Suggested Reading 291
CHAPTER 13 HORMONAL CONTROL OF REPRODUCTION IN THE FEMALE: THE MENSTRUAL CYCLE 292
Female Reproductive Tract 292
OVARIES 292
Folliculogenesis 293
OVIDUCTS AND UTERUS 295
Ovarian Hormones 296
ESTROGENS 296
PROGESTERONE 298
INHIBIN 298
RELAXIN 298
Control of Ovarian Function 298
EFFECTS OF FSH AND LH ON THE DEVELOPING FOLLICLE 299
Estradiol Production 299
Follicular Development 300
Cellular Actions of FSH and LH 300
EFFECTS ON OVULATION 301
EFFECTS ON CORPUS LUTEUM FORMATION 301
EFFECTS ON OOCYTE MATURATION 302
EFFECTS ON CORPUS LUTEAL FUNCTION 302
EFFECTS ON OVARIAN BLOOD FLOW 302
Physiological Actions of Ovarian Steroid Hormones 302
EFFECTS ON THE REPRODUCTIVE TRACT 302
MENSTRUATION 302
EFFECTS ON THE MAMMARY GLANDS 304
OTHER EFFECTS OF OVARIAN HORMONES 304
MECHANISM OF ACTION 304
Regulation of the Reproductive Cycle 305
PATTERN OF HORMONES IN BLOOD DURING THE OVARIAN CYCLE 305
REGULATION OF FSH AND LH SECRETION 306
Negative Feedback Aspects 306
Selection of the Dominant Follicle 307
Positive Feedback Aspects 308
Neural Control of Gonadotropin Secretion 308
Sites of Feedback Control 308
Timing of Reproductive Cycles 310
Suggested Reading 310
CHAPTER 14 HORMONAL CONTROL OF PREGNANCY AND LACTATION 312
Fertilization and Implantation 312
GAMETE TRANSPORT 312
ROLE OF THE OVIDUCTS 313
IMPLANTATION AND THE FORMATION OF THE PLACENTA 314
The Placenta 315
Placental Hormones 316
HUMAN CHORIONIC GONADOTROPIN (HCG) 317
HUMAN CHORIONIC SOMATOMAMMOTROPIN (HCS) 318
PROGESTERONE 319
ESTROGENS 319
The Role of the Fetal Adrenal Cortex 320
The Role of Progesterone and Estrogens in Sustaining Pregnancy 321
Maternal Adaptations to Pregnancy 322
CARDIOVASCULAR ADAPTATIONS 322
RENAL ADAPTATIONS 323
Osmoregulation and Thirst 324
RESPIRATORY ADJUSTMENTS 325
Gas Exchange 325
METABOLIC ADJUSTMENTS 326
CALCIUM BALANCE 326
Parturition 327
THE ROLE OF CORTICOTROPIN RELEASING HORMONE (CRH) 328
THE ROLE OF OXYTOCIN 330
Lactation 330
GROWTH AND DEVELOPMENT OF THE MAMMARY GLANDS 331
MILK PRODUCTION 331
LACTATION AND MATERNAL CALCIUM BALANCE 331
MECHANISM OF PROLACTIN ACTION 332
NEUROENDOCRINE MECHANISMS 333
Milk Let-Down Reflex 333
Cellular Actions of Oxytocin 333
Control of Prolactin Secretion 333
CELLULAR REGULATION OF PROLACTIN SECRETION 335
PROLACTIN IN BLOOD 335
LACTATION AND RESUMPTION OF OVARIAN CYCLES 336
Suggested Reading 336
Index 338
A 338
B 339
C 339
D 339
E 340
F 340
G 340
H 341
I 341
J 341
K 341
L 341
M 342
N 342
O 342
P 342
R 343
S 343
T 344
U 344
V 344
W 344
Z 344