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Hormones -  Gerald Litwack,  Anthony W. Norman

Hormones (eBook)

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2014 | 1. Auflage
822 Seiten
Elsevier Science (Verlag)
978-1-4832-5810-2 (ISBN)
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Hormones provides a comprehensive treatment of human hormones viewed in the light of modern theories of hormone action and in the context of current understanding of subcellular and cellular architecture and classical organ physiology. The book begins with discussions of the first principles of hormone action and the seven classes of steroid hormones and their chemistry, biosynthesis, and metabolism. These are followed by separate chapters that address either a classical endocrine system, e.g., hypothalamic hormones, posterior pituitary hormones, anterior pituitary hormones, ,thyroid hormones, pancreatic hormones, gastrointestinal hormones, calcium regulating hormones, adrenal corticoids, hormones of the adrenal medulla, androgens, estrogens and progestins, and pregnancy and lactation hormones; or newer domains of hormone action which are essential to a comprehensive understanding of hormone action, including prostaglandins, thymus hormones, and pineal hormones. The book concludes with a presentation of hormones of the future, i.e., cell growth factors. This book is intended for use by first-year medical students, graduate students, and advanced undergraduates in the biological sciences. It is also hoped that this book will fill the void that exists for resource materials for teaching cellular and molecular endocrinology and that it will be employed as an equal partner with most standard biochemistry textbooks to provide a comprehensive and balanced coverage of this realm of biology.

Anthony W. Norman received his A.B. from Oberlin College in 1959, and an M.S. and Ph.D. in Biochemistry in 1961 and 1963, respectively, from the University of Wisconsin, Madison. Following postdoctoral work in Paul D. Boyer's group at UCLA, in 1964 he joined the Department of Biochemistry at University of California, Riverside, as an Assistant Professor. From 1976 to 1981 he served as Chair of the department and currently holds a Presidential Chair and is a Distinguished Professor of Biochemistry and Biomedical Sciences. Dr. Norman has also been active for some 25 years in medical education on the UC-Riverside campus and at UCLA through participation in the UR/UCLA Program in Biomedical Sciences, of which he was Dean and Director from 1986 to 1991. Dr. Norman's biomedical research career has focused on the mechanism of action of the vitamin D family of steroids. His chief contributions to these areas of cellular and molecular endocrinology have played a pivotal role in defining the boundaries of this research domain via discoveries that have opened new areas of investigation. The first of these was the discovery in 1968, and chemical characterization in 1971, of the hormonally active form of vitamin D, 1a,25(OH)2-vitamin D3. Subsequent achievements include the discovery and characterization of the nuclear receptor for 1a,25(OH)2D3, the clinical evaluation of 1a,25(OH)2D3 in renal osteodystrophy, articulation of the concept of the vitamin D endocrine system, the importance of 1a,25(OH)2D3 to insulin secretion and the discovery of a new rapid, nongenomic, signal transduction process for 1a,25(OH)2D3. Dr. Norman has been the recipient of awards that include a Fulbright Fellowship, 1970; Public Health Service Career Development Award, 1970; Mead Johnson Award, American Institute of Nutrition, 1977; Ernst Oppenheimer Award, Endocrine Society, 1977; Visiting Lecturer Australian Society of Endocrinology, 1978; Visiting Faculty Member, Mayo Clinic, 1981; Prix Andre.
Hormones provides a comprehensive treatment of human hormones viewed in the light of modern theories of hormone action and in the context of current understanding of subcellular and cellular architecture and classical organ physiology. The book begins with discussions of the first principles of hormone action and the seven classes of steroid hormones and their chemistry, biosynthesis, and metabolism. These are followed by separate chapters that address either a classical endocrine system, e.g., hypothalamic hormones, posterior pituitary hormones, anterior pituitary hormones, ,thyroid hormones, pancreatic hormones, gastrointestinal hormones, calcium regulating hormones, adrenal corticoids, hormones of the adrenal medulla, androgens, estrogens and progestins, and pregnancy and lactation hormones; or newer domains of hormone action which are essential to a comprehensive understanding of hormone action, including prostaglandins, thymus hormones, and pineal hormones. The book concludes with a presentation of hormones of the future, i.e., cell growth factors. This book is intended for use by first-year medical students, graduate students, and advanced undergraduates in the biological sciences. It is also hoped that this book will fill the void that exists for resource materials for teaching cellular and molecular endocrinology and that it will be employed as an equal partner with most standard biochemistry textbooks to provide a comprehensive and balanced coverage of this realm of biology.

Front Cover 1
Hormones 4
Copyright Page 5
Table of Contents 6
Preface 12
Chapter 1. General Considerations of Hormones 18
I. CLASSIFICATION OF HORMONES 19
II. RECEPTORS FOR HORMONES 24
III. MECHANISMS OF HORMONE ACTION 27
IV. EVOLUTION OF HORMONES 56
V. PHYSICAL PARAMETERS OF HORMONE–RECEPTOR INTERACTIONS 57
V. PHYSICAL PARAMETERS OF HORMONE–RECEPTOR INTERACTIONS 57
VI. NEWER DEVELOPMENTS IMPACTING ON THE UNDERSTANDING OF HORMONE ACTION 63
VII. SUMMARY 64
References 64
Chapter 2. Steroid Hormones: Chemistry, Biosynthesis, and Metabolism 66
I. INTRODUCTION 67
II. CHEMISTRY OF STEROIDS 69
III. BIOSYNTHESIS OF CHOLESTEROL 84
IV. BIOSYNTHESIS OF STEROIDS 96
V. PROPERTIES OF ENZYMES INVOLVED IN STEROID METABOLISM 106
VI. CATABOLISM AND EXCRETION OF STEROID HORMONES 111
References 116
Chapter 3. Hypothalamic Regulating Hormones 118
I. INTRODUCTION 118
II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS 122
III. CHEMISTRY 128
IV. BIOCHEMISTRY 134
V. CLINICAL ASPECTS 146
References 147
Chapter 4. 
150 
I. INTRODUCTION 151
II. ANATOMY, DEVELOPMENT, AND FINE STRUCTURE OF THE POSTERIOR PITUITARY 154
III. CHEMISTRY 154
IV. BIOCHEMISTRY 160
V. BIOLOGICAL AND MOLECULAR ACTIONS 167
VI. CLINICAL ASPECTS 183
References 185
Chapter 5. 
188 
I. INTRODUCTION 189
II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS 191
III. CHEMISTRY 200
IV. BIOCHEMISTRY 215
V. PROLACTIN 218
VI. GROWTH HORMONE 221
VII. ß-LIPOTROPIN 227
VIII. THYROTROP1C HORMONE 229
IX. ACTH 231
X. CLINICAL ASPECTS 232
References 234
Chapter 6. 
238 
I. INTRODUCTION 238
II. ANATOMICAL AND MORPHOLOGICAL RELATIONSHIPS 240
III. CHEMISTRY 243
IV. BIOCHEMISTRY 246
V. BIOLOGICAL AND MOLECULAR ACTIONS 270
VI. CLINICAL ASPECTS 276
References 278
Chapter 7. Pancreatic Hormones: Insulin and Glucagon 280
I. INTRODUCTION 281
II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS 289
III. CHEMISTRY 295
IV. BIOCHEMISTRY 303
V. BIOLOGICAL AND MOLECULAR ACTIONS 322
VI. CLINICAL ASPECTS 334
References 336
Chapter 8. Gastrointestinal Hormones 338
I. INTRODUCTION 339
II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS 343
III. CHEMISTRY AND BIOCHEMISTRY 353
IV. BIOLOGICAL AND MOLECULAR ACTIONS 365
V. CLINICAL ASPECTS 369
References 371
Chapter 9. The Calcium-Regulating Hormones: Vitamin D, Parathyroid Hormone, Calcitonin 372
I. INTRODUCTION 373
II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS 377
III. CHEMISTRY AND BIOCHEMISTRY 385
IV. BIOLOGY AND PHYSIOLOGICAL SIGNIFICANCE 396
V. CLINICAL ASPECTS 406
References 412
Chapter 10. 
414 
I. INTRODUCTION 415
II. ANATOMY, DEVELOPMENT, AND CELLULAR FINE STRUCTURE OF THE ADRENAL CORTEX 416
III. CHEMISTRY AND BIOCHEMISTRY 422
IV. BIOLOGICAL AND MOLECULAR ACTIONS 440
V. THE ZONA RETICULARIS AND DEHYDROEPIANDROSTERONE 456
VI. THE MINERALOCORTICOID HORMONE 456
VII. CLINICAL ASPECTS 461
References 464
Chapter 11. Hormones of the Adrenal Medulla 466
I. INTRODUCTION 467
II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIPS 468
III. CHEMISTRY 471
IV. HORMONE ACTION AND BIOCHEMISTRY 476
V. ACTIONS OF EPINEPHRINE 488
VI. ENKEPHALINS 496
VII. CLINICAL ASPECTS 497
References 498
Chapter 12. Androgens 500
I. INTRODUCTION 501
II. ANATOMICAL AND MORPHOLOGICAL RELATIONSHIPS OF THE MALE REPRODUCTIVE SYSTEM 502
III. CHEMISTRY, BIOCHEMISTRY, AND BIOLOGICAL RESPONSES 509
IV. PHYSIOLOGICAL RELATIONSHIPS 516
V. MOLECULAR ACTIONS 521
VI. CLINICAL ASPECTS 525
References 529
Chapter 13. 
532 
I. INTRODUCTION 533
II. ANATOMICAL AND MORPHOLOGICAL RELATIONSHIPS OF THE FEMALE REPRODUCTIVE SYSTEM 534
III. CHEMISTRY, BIOCHEMISTRY, AND BIOLOGICAL RESPONSES 545
IV. PHYSIOLOGICAL RELATIONSHIPS 550
V. BIOLOGICAL AND MOLECULAR ACTIONS 563
VI. CLINICAL ASPECTS 577
References 580
Chapter 14. Hormones of Pregnancy and Lactation 582
I. INTRODUCTION 582
II. ANATOMICAL AND MORPHOLOGICAL RELATIONSHIPS 583
III. CHEMISTRY, BIOCHEMISTRY, AND BIOLOGICAL RESPONSES 591
IV. CELL BIOLOGY AND MOLECULAR ACTIONS 604
V. CLINICAL ASPECTS 620
References 622
Chapter 15. 
624 
I. INTRODUCTION 624
II. ANATOMICAL, MORPHOLOGICAL, AND PHYSIOLOGICAL RELATIONSHIP 627
III. HOMEOSTASIS OF FLUID, ELECTROLYTES, AND BLOOD PRESSURE 632
IV. KALLIKREINS AND KININS 652
V. PROSTAGLANDINS 653
VI. ERYTHROPOIETIN 655
VII. CLINICAL ASPECTS 659
References 660
Chapter 16. Prostaglandins 662
I. INTRODUCTION 663
II. CHEMISTRY 671
III. BIOCHEMISTRY 671
IV. BIOLOGICAL ACTIONS 681
V. LEUKOTRIENES 691
VI. CLINICAL ASPECTS 695
References 696
Chapter 17. 
698 
I. INTRODUCTION 698
II. ANATOMICAL AND MORPHOLOGICAL RELATIONSHIPS 701
III. CELL BIOLOGY 703
IV. CHEMISTRY AND BIOCHEMISTRY 706
V. BIOLOGICAL AND MOLECULAR ACTIONS 712
VI. CLINICAL ASPECTS 714
References 714
Chapter 18. 
716 
I. INTRODUCTION 716
II. ANATOMY AND CELL BIOLOGY 718
III. CHEMISTRY 722
IV. BIOCHEMISTRY 722
V. BIOLOGICAL AND MOLECULAR ACTIONS 730
VI. CLINICAL ASPECTS 733
References 733
Chapter 19. 
736 
I. INTRODUCTION 736
II. ANATOMICAL ASPECTS 742
III. CHEMISTRY 744
IV. BIOCHEMISTR 752
V. CLINICAL ASPECTS 764
References 764
Appendix A: 
766 
Appendix B: Human Blood Concentrations of Major Hormones 775
Appendix C: Clinically Relevant Endocrine Disorders 778
Appendix D: 
783 
Appendix E: Summary of Nobel Prizes in Endocrinology and Related Fields 784
Appendix F: The Genetic Code 786
Appendix G: 
787 
Appendix H: 
788 
Index 790

Preface


The last decades have brought startling advances in our understanding of endocrinology. Of paramount importance is the large increase in the number of legitimate hormones, which now number more than 100, as well as the application of the modern concepts and methodologies of biochemistry and molecular biology to endocrinological research. It is now feasible to approach virtually all classical topics in endocrinology at the cellular and molecular levels.

This book provides a comprehensive treatment of human hormones viewed in the light of modern theories of hormone action and in the context of our current understanding of subcellular and cellular architecture and classical organ physiology. The book is intended for use by first-year medical students, graduate students, and advanced undergraduates in the biological sciences. Also, physicians-in-training should be cognizant of new insights into the etiology of endocrine-related diseases and appreciative of the contribution of basic science to the development of new treatments which are possible through the application of molecular biology and biochemistry to the classic domain of endocrinology. For example, who could have predicted a decade ago that hormonal receptors, or components of hormonal receptors, as well as key cell growth factors could be associated with oncogenes and the cellular expression of certain forms of cancer? Increasingly, medical school curricula are being revised to include a significant coverage of molecular endocrinology. The curriculum for advanced undergraduate biology majors is also being expanded to include molecular endocrinology. Graduate students in medical or biological sciences, including immunology, entomology, genetics, anatomy, physiology, and biochemistry, will inevitably encounter, either in the classroom or in excursions into the modern scientific literature, the contributions and impact of modern endocrinology. It is hoped that this book will fill the void that currently exists for resource materials for teaching cellular and molecular endocrinology and that it will be employed as an equal partner with most standard biochemistry textbooks to provide a comprehensive and balanced coverage of this realm of biology.

Our book presumes that the reader will have been exposed in detail to the fundamental areas of biochemistry, including enzymology, structure and function of macromolecules and the other bioorganic substances of intermediary metabolism, as well as to selected topics in molecular biology. In addition, an understanding of cell biology, cellular and subcellular organization, and mammalian physiology will be useful. It is the tetrad of biochemistry, molecular biology, and cell and organ physiology that provides the principles and biological “facts of life” that are critical to our modern understanding of hormones.

The book provides two introductory chapters followed by seventeen chapters on selected endocrinological topics pertinent to man. The first chapter presents the first principles of hormone action. These include a discussion of the structural and functional classification of hormones and a detailed presentation of current general theories of mechanisms of hormone action at both the cellular and subcellular levels. Chapter 2 provides a detailed presentation of the seven classes of steroid hormones and their chemistry, biosynthesis, and metabolism. These introductory chapters are followed by sixteen chapters that address either a classical endocrine system, e.g., hypothalamic hormones (Chapter 3), posterior pituitary hormones (Chapter 4), anterior pituitary hormones (Chapter 5), thyroid hormones (Chapter 6), pancreatic hormones (Chapter 7), gastrointestinal hormones (Chapter 8), calcium regulating hormones (Chapter 9), adrenal corticoids (Chapter 10), hormones of the adrenal medulla (Chapter 11), androgens (Chapter 12), estrogens and progestins (Chapter 13), hormones of pregnancy and lactation (Chapter 14), or newer domains of hormone action which are now essential to a comprehensive understanding of hormone action, including prostaglandins (Chapter 16), thymus hormones (Chapter 17), and pineal hormones (Chapter 18). The book concludes (Chapter 19) with a presentation of hormones of the future, i.e., cell growth factors. Chapter 15, Hormones of the Kidney, of necessity is not devoted exclusively to a single hormone system; it focuses on the hormones, excluding 1,25-dihydroxyvitamin D (Chapter 9), which are made (erythropoietin, kallikreins) or which act (aldosterone, vasopressin) in the kidney.

Each of the last seventeen chapters is organized in parallel fashion. Thus, each chapter has the following sections: (a) introduction; (b) human anatomical-morphological relationships; (c) chemistry; (d) biochemistry; (e) biological and molecular action of the hormone(s); (f) clinical aspects; and (g) reference citations. The clinical aspects section is not intended to be comprehensive, but rather to provide for the medical student an introduction/resume of key disease states and contemporary medical problems related to the hormone(s) deficiency or excess. In addition, Appendices C and D will provide insight into the definition and incidence rate of prominent endocrine-related disease states. Each chapter is highly illustrated with respect both to human physiology and anatomy and to the details and models of hormone action. Each chapter culminates with a listing of key reference citations, including books and review articles as well as recent research papers.

The book also contains eight appendices: (A) a table listing over 100 hormones; (B) a table of the blood concentrations of major hormones; (C) a list of prominent endocrine disorders; (D) a table of the rate of incidence of principal endocrine disease diagnoses; (E) a tabulation of Nobel prizes awarded in endocrinology and related areas; (F) a table of the genetic code; (G) a table of the three-letter and single-letter abbreviations for amino acids; and (H) a tabulation of the units of scientific measurement.

A major challenge to modern publication techniques as well as to authors is the ability of scientists to obtain the primary amino acid sequence of large proteins/hormones as well as the complementary DNA sequence (cDNA) of nucleotides and genomic sequence of nucleotides for proteins of interest. Thus, modern triumphs of molecular endocrinology include the primary amino acid sequence of prolactin (199 amino acid residues), the cDNA sequence of the steroid receptors for glucocorticoids (4800 nucleotides) and estradiol (3600 nucleotides), as well as the genomic organization of several hormones, e.g., insulin (1720 nucleotides). The dilemma to the authors was whether to include such extensive and detailed information in a volume that is intended for use as a textbook. Clearly, most students will not study protein amino acid sequences or cDNA sequence at the individual amino acid or nucleotide level. Yet we feel it instructive for the student to realize and appreciate the intrinsic complexity and detail of information pertaining to hormones which molecular endocrinologists can now almost routinely achieve. Accordingly, the authors have included many sequences of large peptide hormones as well as cDNA sequences. We have chosen in some instances to limit their format to a single-page “miniprint” rather than to extend their presentation over two or three pages. Interested readers should utilize a magnifying or “reading” glass to facilitate their study (e.g., see Figs. 5-4, 5-7, 7-13, 10-16A, 10-20B, and 13-15).

The text is related to biochemical endocrinology courses we have taught to first-year medical students and graduate students at the University of California–Riverside and Temple University. The authors hope that the uniform organization of the chapters and the subdivision of topics within each chapter will allow instructors to select the level of coverage they require from a comprehensive one to one focusing on only the subcellular mode of action of the hormones. We would like to acknowledge the students at UC-Riverside in Biochemistry 120 who used a draft of this textbook. From their comments and from our co-instructors, Professors H. L. Henry and R. A. Luben, we received much useful feedback.

In addition we would like to thank our professional colleagues who have individually read and critiqued the various chapters. These include: Julius Axelrod (18), Om P. Bahl (5), John D. Baxter (6, 10), Esther Breslow (4), Josiah Brown (6), Ralph A. Bradshaw (19), P. Michael Conn (3), Michael P. Czech (19), Leonard J. Deftos (9), Isidore Edelman (15), John H. Exton (11), H. Hugh Fudenberg (17), W. F. Ganong (3), Jack Geller (12), Allan L. Goldstein (17), Jack Gorski (1), Oscar Hechter (4), Bernard L. Horecker (17), Benita S. Katzenellenbogen (1), Leonard D. Kohn (5), William E. M. Lands (16), Joseph Larner (7), J. B. Lee (16), Robert J. Lefkowitz (11), Choh Hao Li (5), Marc E. Lippman (13), Walter Lovenberg (18), Joseph Meites (3), R. Curtis Morris (9), Allan Munck (10), William D. Odell (14), Jack H. Oppenheimer (6), Peter W. Ramwell (16), Russel J. Reiter (18), Herbert H. Samuels (1, 6), David A. Sirbasku (19), Melvin S. Soloff (4), Donald F. Steiner (97), E. Brad Thompson (10), Sidney Udenfriend (11), Larry Vickery (2), John H. Walsh (8), Owen N. Witte (15), and Richard J. Wurtman (18). We would like to thank Dr. A. Geoffrey Norman, Dr. Valerie Leathers, and Dr. Helen L. Henry, who all read major portions of the...

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