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Benjamin Cummings
Endocrinology / Edition 6

Endocrinology / Edition 6

by Mac Hadley


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Endocrinology / Edition 6

This revision of the classic textbook in endocrinology, Hadley's Endocrinology, offers all of the benefits of previous editions, including clear and authoritative explanations of basic concepts, interesting examples and applications, and detailed coverage of vertebrate hormones. A particular focus is placed on the critical roles of glands, hormones, receptors, and molecular signaling pathways in the control of physiological processes.

Special Features of This New Edition Include: Expanded and updated introductory chapters that present basic concepts of molecular and cellular and integrative endocrinology, Renewed emphasis on neuroendocrinology and reproductive biology, Current coverage of the latest research methodologies in endocrinology, Research updates in every chapter, Examination of recently discovered hormones, Section heads written as declarative, summary sentences to allow easier reading and review, "Think, Analyze, and Review" questions at ends of chapters, Completely new illustration program that features two-color diagrams designed to effectively convey information to students.

Product Details

ISBN-13: 2900131876063
Publisher: Benjamin Cummings
Publication date: 11/07/2006
Edition description: Revised Edition
Pages: 608
Product dimensions: 6.00(w) x 1.25(h) x 9.00(d)

Table of Contents

Preface     xx
Introduction to Endocrinology     1
Endocrine Systems     1
Historical Perspective     2
The Science of Endocrinology Progressed from Simple Observations to Complex Experimentation     2
Berthold's Experiments in Roosters Lead to the Discovery of Testosterone     2
Secretin is Discovered by Bayliss and Starling     3
Insulin is Determined to be a Pancreatic Hormone that Regulates Blood Glucose     4
The Nervous System is Shown to Release Neurotransmitters     4
Sutherland and Colleagues Discover Cyclic AMP     4
Discovery of Hypothalamic Releasing Factors Starts a "Race to Stockholm"     5
Development of Immunoassays Permits Hormone Measurements at Physiological Concentrations     6
Boundaries of Endocrinology are Broadened with the Discovery of Growth Factors     6
Advances in Molecular Biology and Genetics Spawn a New Era in Endocrine Research     6
The Science of Endocrinology     7
The Importance of Comparative Endocrinology is Multidimensional     7
Clinical Endocrinologists Address a Multitude of Important Health Issues     8
The Concept of Homeostasis     8
Homeostatic Systems Use Negative Feedback Control Mechanisms     9
Hormones andHomeostasis     10
Glucose Homeostasis is Controlled by Glucagon and Insulin     10
Calcium Homeostasis is Controlled by Parathyroid Hormone and Calcitonin     10
Sodium Homeostasis is Controlled by the Renin-Angiotensin System and Atriopeptin     11
Neuroendocrine Integration in Homeostasis     12
Neuroendocrine Regulation of Fluid Homeostasis is Mediated by Vasopressin     12
Neuroendocrine Control of Body Temperature is Regulated by Thyroid Hormones and Autonomic Activity     12
Neuroendocrine Control of Energy Homeostasis is Mediated by Neuropeptides and Peripheral Feedback Signals     13
Hormones and Behavior     13
Gonadal Hormones Regulate Reproductive Behaviors     13
Fetal Hormones can "Program" Behavior     14
Hormones, Growth Regulation, and Cancer     14
Review Exercises     14
References     15
The Vertebrate Endocrine System     17
Endocrine Glands and their Hormones     18
Hormones Defined     18
General Classes of Chemical Messengers     22
Protein Hormones Comprise the Most Diverse Family of Chemical Messengers     22
The Thyroid Gland Produces Iodine-Containing Hormones, Thyroxine and Triiodothyronine (T3)     23
Steroid Hormones are Produced Primarily by the Adrenal Cortex and Gonads     24
Many Neurotransmitters are Enzymatically Modified Amino Acids     24
Neuropeptides can Function as Neurohormones, Neurotransmitters, and Neuromodulators     24
Growth Factors are a Diverse Group of Locally Acting Peptide Messengers     25
Eicosanoids are Fatty Acid Derivatives that Include Prostaglandins, Thromboxanes, and Leukotrienes     25
Pheromones are a Diverse Group of Chemical Messengers that Mediate Signaling between Individuals     26
Electrolytes and Metabolites can also Convey Physiological Signals     26
Hormone Synthesis     27
Protein Hormone Synthesis Involves DNA Transcription, mRNA Translation, and Prohormone Processing     27
Steroid Hormones are Derived from Cholesterol     27
Thyroid Hormone Synthesis Requires a Unique Series of Biochemical Processes in Follicular Cells     28
Non-Peptide Neurotransmitters are Synthesized in Nerve Endings     28
Gases can Function as Chemical Messengers     28
Peptide Neurohormones and Neurotransmitters are Synthesized in the Same Manner as Protein Hormones     28
Some Peptide and Steroid Hormones are Derived from Prohormones after Secretion     29
Control of Hormone Secretion     29
Hormone Secretion can be a Regulated or Constitutive Process     29
Secretion of One Hormone is Often Controlled by the Actions of Another     29
Secretions of Some Hormones are Controlled by the Ionic, Metabolic or Hormonal Factors they Regulate     30
Hormone Delivery     31
Hormone Circulation and Metabolism     31
Peptide Hormones Have Short Half-Lives in the Circulation     31
Steroid and Thyroid Hormone are Bound by Globulins that Increase their Half-Lives     32
Adrenal Catecholamines and Neurotransmitters are Enzymatically Inactivated in Liver and Brain, Respectively     33
Physiological Roles of Hormones     33
General Mechanisms of Hormone Action     34
Endocrine Pathophysiology     34
Comparative Endocrinology     35
Review Exercises     36
References     37
General Mechanisms of Hormone Action     39
Cellular Receptors and Hormone Action     39
Hormone Receptors Bind Specific Hormones     40
Tissue Responses to a Hormone are Determined by the Presence of Specific Receptors     41
Some Hormones can Activate Multiple Receptor Isoforms     41
Characteristics of Physiological Receptors     42
Binding assays are Used to Determine the Number, Affinity, and Ligand Specificity of Hormone Receptors     42
Plasma Membrane Hormone Receptors     45
Membrane Receptor Families have Characteristic Structures and Functional Properties     45
Second Messengers of Hormone Action     46
Cyclic Nucleotides Function as Second Messengers in the Actions of Many Hormones     46
Cyclic AMP also Initiates Signaling to the Genome     49
Membrane Receptor Signal Transduction     49
G Proteins Mediate Dual Control of Adenylate Cyclase     50
"Crosstalk" may Occur among Different Signal Transduction Pathways     51
Phosphorylated Proteins as Physiological Effectors     51
Protein Phosphatases also Play Important Roles in Cellular Regulation     52
Multiple Membrane Messengers     52
G Proteins also Couple Receptor Stimulation to Phosphoinositol Hydrolysis     52
Protein Kinase C is a Multifunctional Enzyme that Plays Important Roles in Signal Transduction     53
Eicosanoids and Hormone Action     53
Nuclear Hormone Receptors     57
Steroid/Thyroid Hormone Receptors     57
Direct Membrane Actions of Steroid Hormone     59
Permissive, Additive, and Synergistic Actions of Hormones     59
Receptor Regulation     61
Hormones can Regulate Receptor Number      61
Receptor cooperativity Can Modulate Responses to Hormones     62
"Spare Receptors" are Commonly Present in Hormone-Responsive Cells     62
Termination of Hormone Action     62
Pathophysiological Correlates of Hormone Action     62
Review Exercises     64
References     65
Endocrine Methodologies     67
General Considerations     67
What Do Endocrinologists Want to Know about a Hormone?     68
Surgical Methods     69
Hormone Replacement Therapy     69
Immunological Neutralization of Hormone Activity     70
Tissue Extracts and Purification     70
Chemical Identification and Synthesis     71
Histological-Cytological Studies     71
Immunohistochemistry can be Used to Visualize the Expression Pattern of a Hormone or Receptor     72
Assay Methodologies     74
Bioassays Measure Levels of a Hormone on the Basis of its Biological Activity     74
Bioassays can be Used in Conjunction with Structure-Activity Analyses     75
Bioassays are Used with Site-Directed Mutagenesis to Analyze Functional Domains of Hormone Receptors     75
Radioimmunoassays Measure Levels of a Hormone on the Basis of its Antigenic Properties      75
Non-Radioisotopic Immunoassays are Now Widely Used by Endocrine Researchers and Clinicians     76
Analysis of Hormone Actions     77
Radioisotopes can be Used to Assay Cellular Responses to a Hormone     77
Radioligand Binding Assays Assess Physiological Regulation of Hormone Receptor Number or Affinity     77
Immunoblots Permit Analysis of Specific Proteins in Hormone-Responsive Cells     78
Some Cellular Responses to Hormones can be Assessed by Enzyme Assays     78
Autoradiographic Techniques Determine the Cellular Site of Radiolabeled Substrate Incorporation     78
Analysis of Gene Expression in Endocrine Systems     79
Steady-State mRNA levels are Analyzed as a Measure of Gene Expression     80
Tissue- and Cell-Specific mRNA Expression Patterns are Analyzed by In Situ Hybridization     82
Hormone Effects on Gene Expression can be Profiled using DNA Microarrays     82
Transcriptional Regulation can be Studied using Reporter Gene Constructs     82
Electrophysiological Methods     83
Pharmacological Methods     83
Behavioral Methods     84
Recombinant DNA Techniques     85
Genetic Engineering     86
Animal Models for Research     88
Cyclostomes      88
Cartilaginous Fishes     88
Bony Fishes     88
Amphibians     88
Reptiles     89
Birds     89
Nonprimate Mammals     89
Primates     89
Animal Welfare     89
Perspectives     90
Review Exercises     90
References     91
Pituitary Hormones     93
Anatomy of the Pituitary Gland     94
The Adenohypophysis and Neurohypophysis have Separate Embryonic Origins     94
Lobation, vascularization, and Innervation of the Pituitary can Differ among Species     96
Cytological Methods Distinguish Different Pituitary Cell Types     97
Hormones of the Pituitary     98
Pituitary Hormones can be Grouped into Families of Structurally Related Proteins     98
Growth Hormone and Prolactin are Structurally Related Hormones that Stimulate Growth and Development     98
Luteinizing Hormone, Follicle-Stimulating Hormone, and Thyrotropin are Glycoprotein Hormones     102
Corticotropin and Melanotropins are Hormones Derived from a Common Precursor, Proopiomelanocortin     104
Vasopressin and Oxytocin are the Major Neurohypophysial Hormones     106
Pituitary Pathophysiology     106
Molecular Medicine Case Studies     108
Review Exercises     108
References     109
The Endocrine Hypothalamus     111
The Neurovascular Hypothesis     111
Structure-Function of the Endocrine Hypothalamus     112
The Hypophysiotropic Hormones     114
Thyrotropin-Releasing Hormone (TRH) Stimulates Synthesis and Secretion of TSH     115
Somatostatin (SST) Inhibits GH Secretion from Somatotrophs     116
GH-Releasing Hormone and Ghrelin Stimulate GH Secretion     117
Gonadotropin-Releasing Hormone (GnRH) Stimulates LH and FSH Secretion from Gonadotrophs     117
Corticotropin-Releasing Hormone (CRH) Stimulates ACTH Secretion from Corticotrophs     119
Dopamine is a Major Prolactin-Release-Inhibiting Factor (PIF)     120
A Physiological Prolactin-Releasing Factor (PRF) has yet to be Demonstrated     120
Dopamine May Function as an MSH Release-Inhibiting Factor (MIF)     120
Control of Hypothalamic/Hypophysial Hormone Secretion     121
Neurohormone Secretions are Governed by Central Neurons and their Neurotransmitters     121
Specific Neurotransmitters Regulate Hypophysiotropin Secretions     122
Peripheral Hormones Exert Feedback Actions in the Hypothalamus     123
Hypophysiotropic Hormones are Usually Secreted in a Rhythmic Pattern     126
Neuropharmacological Agents are Used to Probe the Neural Regulation of Hypophysiotropin Release     126
Mechanisms of Hypophysiotropin Action     127
Steroid and Thyroid Hormones can Directly Modulate Pituitary Hormone Secretion     128
Pathophysiology of Hypothalamic Dysfunction     128
Molecular Medicine Case Study     130
Conclusions and Speculations     130
Review Exercises     131
References     132
Neurohypophysial Hormones     134
The Neurohypophysis     134
Synthesis and Chemistry     135
Control of Neurohypophysial Hormone Secretion     138
Physiological Roles     138
Oxytocin Controls Milk Release and Uterine Contractions     139
Vasopressin (AVP) Mediates Osmoregulation and Blood Pressure Responses     143
Vasotocin (AVT) is a Major Nonapeptide Hormone in Nonmammalian Vertebrates     146
Circulation and Metabolism     147
Mechanisms of Hormone Action     147
Pathophysiology     150
Evolution of the Neurohypophysial Hormones     152
Other Neurohypophysial Hormones     152
Molecular Medicine Case Studies      154
Review Exercises     154
References     155
Opiomelanocortins     157
Proopiomelanocortin (POMC): A Multifunctional Precursor     157
The Pars Intermedia: A Source of Melanotropins     159
Control of MSH Secretion     159
Physiological Roles of MSH     163
MSH Regulates Melanin Pigmentation of the Skin     163
Melanocortin Receptors Regulate Animal Pigmentation     165
MSH Directs Color Changes in Nonmammalian Vertebrates     167
Other Roles of Melanocortins     167
Mechanism of MSH Action     169
Analogs of Melanotropins are Analyzed in Structure-Function Studies     171
Melanin-Concentrating Hormone     172
Pathophysiologies Involving Melanotropic Hormones can Accompany other Endocrinopathies     174
Biomedical Applications of Melanocortins are in Development     174
The Endorphins     174
Endogenous Opioid Peptides are Derived from POMC, Proenkephalin, and Prodynorphin     175
The Physiological Roles of Opioid Peptides are Remarkably Diverse     176
Opioid Peptides Modulate Neuronal Activity through the [delta], [mgr], and [Kcy] Classes of Opioid Receptors     177
Opioid Peptide Systems are Involved in the Pathophysiology of Drug Addiction     178
Review Exercises     179
References     179
Hormonal Control of Calcium Homeostasis     182
Calcium and Bone Physiology     182
Parathormone     183
The "Chief Cells" of the Parathyroid Glands Secrete Parathormone     183
Parathormone Acts to Raise Plasma Ca[superscript 2+] Levels     185
Parathormone-Relaled Peptide (PTHrP)     186
Calcitonin     187
The Parafollicular Cells of the Thyroid Secrete Calcitonin     187
Calcitonin Acts to Lower Plasma Ca[superscript 2+] Levels     188
Vitamin D     189
Vitamin D is Produced by a Pathway that Involves the Skin, Liver, and Kidneys     189
Vitamin D Promotes Ca[superscript 2+] Absorption in the Gut and Ca[superscript 2+] Reabsorption in the Kidney     193
Hormone Mechanisms of Action in Calcium Homeostasis     194
Parathormone, Calcitonin, and Vitamin D Activate their Cognate Receptors in Multiple Tissues     194
Hormone Integration in Calcium Homeostasis     196
Hormonal Regulation of Intracellular Calcium     198
Calmodulin is an Intracellular Calcium Receptor     199
Pathophysiology     201
Hypoparathyroidism Results in Hypocalcemia      201
Hyperparathyroidism Results in Hypercalcemia     202
Hypercalcemia can Accompany Some Malignancies     203
Osteomalacia is a Condition of Inadequate Bone Mineralization     204
Paget's Disease is Characterized by Excess Osteoclastic Activity     204
Osteoporosis is a Condition of Decreased Bone Mineral Density     205
New Pharmacological Therapies for Diseases of Ca[superscript 2+] Homeostasis are Available     207
Molecular Medicine Case Studies     207
Review Exercises     208
References     209
Gastrointestinal Hormones     211
Gastrointestinal Tract Structure and Function     211
Source and Chemistry of the Gastrointestinal Hormones     212
Gastrin Hormone Family Members Contain a Biologically Active C-Terminal Pentapeptide Sequence     213
Secretin Shares Partial Sequence Identity with Glucagon, GIP, and VIP     214
The GI Tract Produces other Biologically Active Peptides that are Putative Hormones     215
Physiological Roles of the Gastrointestinal Hormones     215
Gastrin Stimulates Acid Secretion in the Stomach     215
Secretin Stimulates Pancreatic Bicarbonate and Enzyme Secretions     217
Cholecystokinin (CCK) Stimulates Gallbladder Contraction and Pancreatic Enzyme Secretions      218
Gastric Inhibitory Peptide (GIP) Inhibits Gastric Emptying and Gastric Acid Secretion     219
Glucagon-Like Peptide-1 (GLP-1) Stimulates Insulin Secretion and Inhibits Glucagon Secretion     220
Vasoactive Intestinal Peptide (VIP) Inhibits Gastric Acid Secretion and Stimulates Pancreatic Electrolyte and Water Secretion     220
Neurotensin Stimulates Pancreatic Secretion and Inhibits Gastric Motility     221
Peptide YY Inhibits Pancreatic Bicarbonate Secretion, Gallbladder Contraction, and Gastric Emptying     221
Substance P (SP) May Serve as a Physiological Modulator of Intestinal Smooth Muscle Contractility     222
Somatostatin Inhibits Gastrin and Hydrochloric Acid Release     222
Gastrin-Releasing Peptide (GRP) Stimulates Release of Several GI Hormones, Pancreatic Secretion, and Motility     223
Motilin Stimulates GI Motility and Emptying of Chyme into the Small Intestine     224
Ghrelin is a Multifunctional Peptide that Stimulates Gastric Acid Secretion and Gastric Motility     224
Other Putative Gut Hormones Exert Specific Actions in the GI Tract     224
Autonomic Nervous System Control of GI Function     226
Gastrointestinal Hormone Mechanisms of Action     227
Integrated Actions of Gastrin, Acetylcholine and Histamine Control Gastric Acid Secretion     227
Synergistic Actions of Secretin and CCK Control Exocrine Pancreatic Secretion     227
The GI hormones can also Exert Trophic Actions     228
Summary of the Neuroendocrine Control of GI Function     228
Pathophysiology     229
Evolutionary Relationships of the Gut hormones     231
Perspectives     234
Review Exercises     234
References     235
Pancreatic Hormones and Metabolic Regulation     237
The Endocrine Pancreas     237
Intermediary Metabolism     239
Insulin     241
Insulin Consists of Two Polypeptide Chains Derived from a Single Preprohormone     241
Insulin Regulates Carbohydrate, Fat, and Protein Metabolism in Many Target Tissues     243
Insulin's Actions are Mediated by a Receptor Tyrosine Kinase     243
Glucagon     247
Glucagon is Structurally Related to Secretin, GIP, and VIP     247
Glucagon Stimulates Glycogenolysis, Gluconeogenesis, and Lipolysis     248
Glucagon Activates Receptors Coupled to cAMP Formation in Hepatocytes and Adipocytes     248
Other Pancreatic Peptide Hormones     249
Somatostatin (SST) is Secreted by Pancreatic D Cells     249
Pancreatic Polypeptide (PP) is Secreted by Pancreatic F Cells      250
Adipocytokines     256
Leptin is an Adiposity Signal that Suppresses Food Intake     251
Adiponectin is an Endogenous Insulin-Sensitizing Factor     251
Resistin can Induce Hepatic Insulin Resistance     251
Control of Pancreatic Islet Function     252
Glucose Counterregulation is Mediated by Several Different Hormones     254
Neuroendocrine Regulation of Food Intake and Body Weight     255
Pancreatic Islet Pathophysiology     255
Insulin-Dependent and Non-Insulin-Dependent Diabetes Mellitus Have Different Etiologies     256
Obesity can Cause Insulin Resistance and Dysregulation of Insulin Secretion, Leading to NIDDM     259
Malignancies of Pancreatic Islet Cells can Cause Profound Metabolic Disturbances     260
Improved Insulin Replacement Therapies are Being Explored     261
Review Exercises     262
References     262
Growth Hormones     264
Growth and Cellular Proliferation     264
Growth Hormone and flie Somatomedins     265
Insulin     273
Prolactin     274
Placental Lactogen     274
Neurotropic Growth Factors     275
NGF Promotes Survival of Peripheral Sympathetic and Spinal Neurons During Development     275
NGF is one Member of a Family of Neurotropins     277
Apoptosis can be Triggered by Some Growth Factors and Hormones     278
Hematopoietic Growth Factors     279
Erythropoietin Enhances the Formation of New Red Blood Cells     279
Thymic Hormones Stimulate Maturation of T Lymphocytes     282
Platelet-Derived Growth Factor (PDGF) Acts Locally on Injured Blood Vessels     284
Other Peptide Growth Factors     284
Epidermal Growth Factor Stimulates Proliferation and Keratinization of Epidermal Tissue     284
Tumor-Derived Growth Factors also Play Important Roles in Normal Development     286
Cytokines can have Both Immunological and Physiological Functions     289
Chalones are Mitotic Inhibitors     289
Growth Factors, Receptors, and Cancer     289
Review Exercises     290
References     291
Thyroid Hormones     293
The Thyroid Gland     293
Synthesis and Chemistry     295
Thyrotropin Induces Expression and Activation of Proteins Controlling Thyroid Hormone Synthesis     295
Antithyroid Drugs can Suppress Thyroid Hormone Synthesis     297
Thyroid Hormones or Thyroid Hormone?     298
Other Iodothyronines in Biological Fluids     298
Control of Thyroid Hormone Secretion     299
Circulation and Metabolism     299
Physiological Roles     300
Thyroid Hormones are Required for Normal Growth and Development     300
Thyroid Hormones Stimulate Thermogenesis and Oxygen Consumption     301
Diet can Alter Thyroid Hormone Production and Function     301
Many Actions of Thyroid Hormones are "Permissive"     302
Mechanisms of Action     302
Pathophyaiology     304
Molecular Medicine Case Studies     308
Comparative Endocrinology     310
Thyroid Hormones Play Additional Roles in Other Vertebrates     312
Review Exercises     312
References     313
Catecholamines and the Sympathoadrenal System     315
Historical Perspective     315
The Sympathoadrenal System     316
The Autonomic Nervous System Includes Sympathetic and Parasympathetic Divsions     317
The Adrenal Medulla is Comprised of Chromaffin Tissue     317
Adrenal Chomaffin Cell Development Depends on Both Genetic Programming and Environmental Cues     319
Synthesis, Chemistry, and Metabolism of Catecholamines     320
Sympathoadrenal System Receptors      322
Nicotinic and Muscarinic Cholinergic Receptors are Pharmacologically and Structurally Distinct     322
Adrenergic Receptors (Adrenoceptors) Mediate the Actions of Norepinephrine and Epinephrine     323
Adrenoceptor Structure     325
Adrenoceptor Signal Transduction     326
Hormonal Modulation of Adrenoceptors     328
Sympathoadrenal Functions     329
Catecholamines Regulate Intermediary Metabolism     330
The Sympathetic Nervous System Regulates Thermogenesis     331
Adrenergic Receptors Mediate Cardiovascular Responses to Stress     331
[Beta]-Adrenergic Receptors Mediate Dilation of Bronchial Passageways     332
Sympathoadrenal, Hypothalamic-Pituitary-Adrenal, and Parasympathetic Stress Responses are Integrated     332
Norepinephrine may Function as Both Neurotransmitter and Hormone in Humans     332
Sympathoadrenal Pathophysiology     332
Comparative Endocrinology     333
Review Exercises     334
References     335
Adrenal Steroid Hormones     337
Historical Perspective     337
The Adrenal Glands     338
Adrenomedullary and Adrenocortical Tissues have Separate Embryological Origins     338
Histology      339
The Fetal Adrenal Cortex Regresses Towards the End of Gestation     340
Chemistry and Synthesis     340
The Adrenal Cortex is Composed of Three Separate Functional Zones     344
Control of Synthesis and Secretion     344
Pituitary ACTH Regulates the Synthesis and Secretion of Glucocorticoids     344
Aldosterone Synthesis and Secretion is Regulated by the Renin-Angiotensin System     345
A Renal Kallikrein-Kinin System Activates Vasoactive Peptides     347
An Atrial Natriuretic Factor (ANF) Inhibits Renal Tubular Reabsorption     348
Circulation and Metabolism     350
Physiological Roles     351
Glucocorticoids Regulate Key Physiological Processes in Response to Prolonged Stress     351
Aldosterone Stimulates Sodium Reabsorption in Renal Tubules     354
Physiological Roles of Adrenal Androgens have yet to be Clarified     355
Mechanisms of Action     355
Glucocorticoids Exert Actions Through Intracellular Glucocorticoid Receptors     355
Aldosterone's Actions are Mediated by Intracellular Mineralocorticoid Receptors     356
Angiotensin II Actions are Mediated by Cognate G-Protein-Coupled Receptors, AT[subscript 1] and AT[subscript 2]     357
Pathophysiology     357
Disorders of Cortisol Secretion Include Syndromes of Cortisol Deficiency and Excess     357
Disorders of Aldosterone Secretion Include Syndromes of Aldosterone Excess or Deficiency     360
Disorders of Steroid Secretion can be Caused by Genetic Mutations Producing Adrenal Enzyme Defects     361
Defects in LDL Receptor Function are Linked to Development of Atherosclerosis     362
Adrenal Steroid Hormone Pharmacology     363
Review Excercises     364
References     364
Endocrinology of Sex Differentiation and Development     366
Sex Determination, Differentiation, and Development     366
Sex Chromosomes Define Genetic Sex     366
Gonadal Sex is Determined by SRY Gene Expression in the Male, and its Absence in the Female     367
Phenotypric Sex of the Genital Ducts Depends on the Presence or Absence of AMH and Androgens     369
Phenotypic Sex of the External Genitaha Depends on the Presence or Absence of Androgens     370
Gonadal Steroid Hormone Synthesis and Chemistry     370
Gonadal Steroids and Brain Differentiation     373
Organizational Effects of Androgens Mediate Male-Type Brain Development     373
Activational Effects of Gonadal Steroids Evoke Acute Neuroendocrine and Behavioral Responses     375
Puberty      378
Precocious and Delayed Puberty can have Constitutional or Pathophysiological Origins     378
Pubertal Development is Driven by an Activation of the Hypothalamic "GnRH Pulse Generator"     379
Pathophysiology of Sex Differentiation and Development     380
Gonadal Dysgenesis is a Failure of Normal Gonadal Differentiation     381
Pseudohermaphroditism can Result from Defects in Fetal Steroid Synthesis or End-Organ Resistance     381
Hypogonadism and Hypergonadism can have Gonadal, Pituitary, or Hypothalamic Bases     382
Molecular Medicine Case Study     384
Review Exercises     384
References     385
Hormones and Male Reproductive Physiology     387
Anatomy of the Male Reproductive System     387
The Major Functions of the Testes are Spermatogenesis and Steroidogenesis     388
Source, Synthesis, Chemistry, and Metabolism of Androgens     388
Endocrine Control of Testicular Function     389
Male Reproductive Function is Maintained by a "Hypothalamic-Pituitary-Testicular Axis" of Hormones     389
Inhibin Exerts Negative Feedback Actions on Pituitary FSH Secretion     390
Prolactin can Regulate LH Receptor Number in Leydig Cells     391
Physiological Roles of Androgens     392
Spermatogenesis Depends on Both FSH and Testosterone     392
Testosterone Acts at Several Neural Loci to Modulate Reproductive Behavior and Sexual Function     393
Hormone Actions in the Fetal Brain may Program Sexual Orientation     394
Testosterone Stimulates Development of Male Secondary Sex Characteristics     395
Androgens Exert Anabolic Actions in Muscle, Cartilage and other Target Tissues     397
Serum Testosterone Levels Decline in Aging Men     397
Physiological Roles of Estrogens     398
Mechanisms of Androgen Action     398
Pathophysiology     400
Molecular Medicine Case Study     404
Review Exercises     405
References     405
Hormones and Female Reproductive Physiology     408
Anatomy of the Female Reproductive System     408
The Major Physiological Activities of the Ovary are Hormonogenesis and Gametogenesis     409
Fallopian Tubes Convey Ova Towards the Uterus     413
The Uterus is the Site of Implantation of a Fertilized Egg and Fetal Development     413
Ovarian Steroid Hormones     413
Estrogen Biosynthesis Requires Androgen Production in Thecal Cells and Aromatization in Granulosa Cells     413
Progesterone Biosynthesis Occurs Primarily in Luteal Cells      414
Androgens May Support some Aspects of Female Pubertal Maturation     415
Paracrine-Acting Growth Factors Regulate Ovarian Function     415
Physiological Roles of Ovarian Steroid Hormones     416
Mechanisms of Action of Ovarian Steroid Hormones     417
Two Estrogen Receptor Isoforms (ER[alpha], ER[Beta]) Mediate Genomic Actions of Estrogen     417
Progesterone's Genomic Actions are Mediated by Progesterone Receptors A and B (PR[subscript A], PR[subscript B])     418
Neuroendocrine Control of Ovarian Function     418
A Neural "GnRH Pulse Generator" Directs Pituitary Gonadotropin Secretion     420
Menstrual Cyclicity is Maintained by Ovarian Feedback Mechanisms     421
Intrafollicular Polypeptides Regulate Folliculogenesis and Oocyte Maturation     422
Mammalian Reprodactive Cycles     423
The Primate Menstrual Cycle is Orchestrated by Cyclic Secretions of Pituitary and Gonadal Hormones     423
Females of Various Animal Species may be Induced or Spontaneous Ovulators     426
Delayed Implantation is an Adaptive Mechanism that Permits Optimal Timing of Birth     426
Environmental Cues can Regulate the Timing of Reproduction     427
Pathophysiology     429
Molecular Medicine Case Studies     431
Review Exercises      432
References     433
Endocrinology of Pregnancy, Parturition, and Lactation     436
Oviparity, Ovoviparity, and Viriparity     436
Pregnancy     436
Fertilization of the Egg and Implantation of the Blastocyst Initiates Development of the Fetal-Placental Unit     436
hCG Rescues the Corpus Luteum     437
The Placenta Assumes the Role of an Endocrine Organ     438
Parturition     440
Neural and Endocrine Mechanisms Control of Parturition     440
A Mechanistic Understanding of Labor Initiation in Humans Remains Elusive     443
Lactation     444
Hormonal Contraception     447
Menopause     449
Pathophysiology     451
Review Exercises     452
References     453
Endocrine Role of the Pineal Gland     455
Pineal Development and Morphology     455
The Melatonin Hypthosis     456
Early Observations Suggested that the Pineal can Influence Reproductive Function     456
Studies in Hamsters have Provided Important Information on Pineal Function     457
Pineal Indoleamine Biosynthesis     459
The Rhythm of Melatonin Production is Affected by Light     459
The Suprachiasmatic Nucleus Controls Pineal Melatonin Release through a Multi-Synaptic Pathway     460
Norepinephrine Regulates Melatonin Biosynthesis via [Beta[subscript 1]]-Adrenergic Receptors     461
Melatonin Secretion and Circulation     462
Site of Action of Melatonin     462
Pineal Rhythms and Biological Clocks     464
Pathophysiology     466
Melatonin Effects on Humans     467
Other Proposed Roles of the Pineal     468
The Pineal Gland in Birds is Directly Light-Sensitive     469
The Pineal Glands of Poikilotherms are also Photosensitive     469
The Pineal Gland and Melatonin Release Control Chromatophores in Poikilothermic Vertebrates     470
Melatonin Mechanisms of Action     470
Review Exercises     471
References     472
Answers to Review Exercises     474
Bibliography     483
Index     486

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