ndocrinology Basic and Clinical Principles Shlomo Melmed P. Michael Conn e ndocrinology Basic and Clinical Principles SECOND EDITION SECOND EDITION Shlomo Melmed P. Michael Conn ENDOCRINOLOGY E NDOCRINOLOGY Basic and Clinical Principles S ECOND E DITION Edited by SHLOMO MELMED, MD Cedars Sinai Medical Center and UCLA School of Medicine P. M ICHAEL CONN, PhD Oregon Health & Science University Beaverton, OR © 2005 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel.: 973-256-1699; Fax: 973-256-8341, E-mail: orders@humanapr.com; or visit our Website: http://humanapress.com All rights reserved. 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Includes bibliographical references and index. ISBN 1-58829-427-7 (alk. paper) eISBN 1-59259-829-3 1. Endocrinology. 2. Hormones. 3. Endocrine glands—Diseases. I. Melmed, Shlomo. II. Conn, P. Michael. QP187.E555 2005 612.4—dc22 2004018638 v Endocrinology: Basic and Clinical Principles, Sec- ond Edition aims to provide a comprehensive knowl- edge base for the applied and clinical science of endocrinology. The challenge in its presentation was to produce a volume that was timely, provided integra- tion of basic science with physiologic and clinical prin- ciples, and yet was limited to 500 pages. This length makes the volume suitable as a text; and the timeliness we have striven for allows the book to serve as an off- the-shelf reference. Our goal was achieved largely through the selection of authors who are both expert writers and teachers. Tables and illustrative matter were used optimally to present information in a con- cise and comparative format. Endocrinology: Basic and Clinical Principles, Sec- ond Edition will be useful to physicians and scientists as well as to students who wish to have a high-quality, PREFACE current reference to the general field of endocrinology. The use of an outline system and a comprehensive index will allow readers to locate promptly topics of particu- lar interest. Key references are provided throughout for individuals requiring more in-depth information. The volume covers the comprehensive spectrum of current knowledge of hormone production and action, even including nonmammalian systems and plants, coverage rarely included in similar volumes. The editors wish to express appreciation to our dis- tinguished chapter authors for their efforts, as well as diligently meeting publication deadlines and to the staff at Humana Press for their cooperation and useful sug- gestions. Shlomo Melmed P. Michael Conn Preface vii Contributors ix Value Added eBook xi PART I. INTRODUCTION 1 Introduction to Endocrinology 3 P. Michael Conn PART II. HORMONE SECRETION AND ACTION 2 Receptors: Molecular Mediators of Hormone Action 9 Kelly E. Mayo 3 Second-Messenger Systems and Signal Transduction Mechanisms 35 Eliot R. Spindel 4 Steroid Hormones 49 Derek Henley, Jonathan Lindzey, and Kenneth S. Korach 5 Plasma Membrane Receptors for Steroid Hormones in Cell Signaling and Nuclear Function 67 Richard J. Pietras and Clara M. Szego 6 Growth Factors 85 Derek LeRoith and William L. Lowe Jr. 7 Prostaglandins and Leukotrienes: Locally Acting Agents 93 John A. McCracken 8 The Neuroendocrine–Immune Interface 113 Michael S. Harbuz and Stafford L. Lightman Part III. Insects/Plants/Comparative 9 Insect Hormones 127 Lawrence I. Gilbert 10 Phytohormones and Signal Transduction Pathways in Plants 137 William Teale, Ivan Paponov, Olaf Tietz, and Klaus Palme 11 Comparative Endocrinology 149 Fredrick Stormshak vii CONTENTS Part IV. Hypothalamic–Pituitary 12 Hypothalamic Hormones: GnRH, TRH, GHRH, SRIF, CRH, and Dopamine 173 Constantine A. Stratakis and George P. Chrousos 13 Anterior Pituitary Hormones 197 Ilan Shimon and Shlomo Melmed 14 Posterior Pituitary Hormones 211 Daniel G. Bichet 15 Endocrine Disease: Value for Understanding Hormonal Actions 233 Anthony P. Heaney and Glenn D. Braunstein 16 The Pineal Hormone (Melatonin) 255 Irina V. Zhdanova and Richard J. Wurtman 17 Thyroid Hormones (T 4 , T 3 ) 267 Takahiko Kogai and Gregory A. Brent 18 Calcium-Regulating Hormones: Vitamin D and Parathyroid Hormone 283 Geoffrey N. Hendy 19 Oncogenes and Tumor Suppressor Genes in Tumorigenesis of the Endocrine System 301 Anthony P. Heaney and Shlomo Melmed 20 Insulin Secretion and Action 311 Run Yu, Hongxiang Hui, and Shlomo Melmed 21 Cardiovascular Hormones 321 Willis K. Samson and Meghan M. Taylor 22 Adrenal Medulla (Catecholamines and Peptides) 337 William J. Raum 23 Hormones of the Kidney 353 Masashi Mukoyama and Kazuwa Nakao 24 Reproduction and Fertility 367 Neena B. Schwartz 25 Endocrinology of Fat, Metabolism, and Appetite 375 Rachel L. Batterham and Michael A. Cowley 26 Endocrinology of the Ovary 391 Denis Magoffin, Ashim Kumar, Bulent Yildiz, and Ricardo Azziz 27 The Testis 405 Amiya Sinha Hikim, Ronald S. Swerdloff, and Christina Wang 28 Endocrinology of Aging 419 Steven W. J. Lamberts Index 429 Contents viii ix RICARDO AZZIZ, MD, MPH, MBA • Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA R ACHEL L. BATTERHAM, MBBS, PhD • University College London, London, UK D ANIEL G. BICHET, MD • Clinical Research Unit and Nephrology Service, Hospital du Sacre-Coeur de Montreal, Montreal, Canada G LENN D. BRAUNSTEIN, MD • Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA G REGORY A. BRENT, MD • Departments of Medicine and Physiology, UCLA School of Medicine, Los Angeles, CA G EORGE P. CHROUSOS, PhD • National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD P. M ICHAEL CONN, PhD • Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR M ICHAEL A. COWLEY, PhD • Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR L AWRENCE I. GILBERT, PhD • Department of Biology, University of North Carolina, Chapel Hill, NC MICHAEL S. HARBUZ, PhD • Department of Medicine, Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, UK A NTHONY P. HEANEY, MD, PhD • Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA GEOFFREY N. HENDY, PhD • Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Canada D EREK V. HENLEY, PhD • Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC A MIYA SINHA HIKIM, PhD • Division of Endocrinology, Department of Medicine, Harbor-UCLA Medical Center and Education and Research Institute, UCLA School of Medicine, Torrance, CA CONTRIBUTORS HONGXIANG HUI, MD, PhD • Division of Endocrinology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA T AKAHIKO KOGAI, MD, PhD • Division of Endocrinology and Diabetes, VA Greater Los Angeles Healthcare System, UCLA School of Medicine, Los Angeles, CA K ENNETH S. KORACH, PhD • Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC A SHIM KUMAR, MD • Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA S TEVEN W. J. LAMBERTS, MD, PhD • Department of Medicine, Erasmus Medical Center, Rotterdam, The Netherlands D EREK LEROITH, MD, PhD • Diabetes Branch, National Institutes of Health, Bethesda, MA STAFFORD L. LIGHTMAN, PhD • Department of Medicine, Henry Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, UK J ONATHAN LINDZEY, PhD • Department of Natural Sciences, Clayton College and State University, Morrow, GA W ILLIAM L. LOWE JR., MD • Department of Medicine, Northwestern University Medical School, Chicago, IL D ENIS MAGOFFIN, PhD • Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA K ELLY E. MAYO, PhD • Department of Biochemistry, Molecular Biology, and Cell Biology, Center for Reproductive Science, Northwestern University, Evanston, IL JOHN A. MCCRACKEN, PhD • University of Connecticut, Storrs, CT S HLOMO MELMED, MD • Division of Endocrinology and Metabolism, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA M ASASHI MUKOYAMA, MD, PhD • Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan [...]... receptor and the nucleus Smads 1, 2, 3, 5, and 8 are known as receptorregulated Smads (R-Smads), and they are direct targets for phosphorylation within a C-terminal SSXS motif by the type I receptor The TGF-β-related ligands lead to phosphorylation of Smads 2 and 3, and the BMP-related ligands lead to phosphorylation of Smads 1, 5, and 8 The phosphorylated Smad proteins dissociate from the receptor and. .. enzyme adenylyl cyclase and thereby regulate production of the second-messenger cAMP (Schramm and Selinger, 19 84), and Gq and G 11 class G proteins regulate phopholipase Cβ activity 14 and control the production of inositol phosphate, diacylglycerol, and calcium second messengers (Berridge, 19 93) Both the α and βγ G protein subunits regulate enzyme effectors, and a cycle of GTP binding and subsequent hydrolysis... contact Humana Press eBook Support by e-mail at ebooksupport@humanapr.com or by phone at 97 3-2 5 616 99 *Adobe and Reader are either registered trademarks or trademarks of Adobe Systems Incorporated in the United States and/ or other countries xi Chapter 1 / Short Chapter Title PART I INTRODUCTION 1 2 Part I / Introduction Chapter 1 / Short Chapter Title 3 1 Introduction to Endocrinology P Michael Conn, PhD... activity, conserved membrane-proximal regions of their Part II / Hormone Secretion and Action cytoplasmic domains mediate ligand-dependent interaction with one or more cytoplasmic protein tyrosine kinases, the Janus kinases, or Jaks (Ihle and Kerr, 19 95) These kinases, including Jak1, Jak2, Jak3, and Tyk2, have amino-terminal homology domains of unknown function, and two carboxyl-terminal kinase domains,... receptors because of their mem- 16 16 Part II / Hormone Secretion and Action Fig 4 Structure and signal transduction by GPCRs (A) Major families and groups of GPCRs (GCPR Database; Horn et al 2003) The mammalian receptors are largely confined to families A, B, and C Family A is the largest and includes the diverse odorant receptors as well as prototypic GPCRs such as rhodopsin and the β-adrenergic receptor... G proteins are a large family of guanosine 5´-triphosphate (GTP)-binding proteins that are heterotrimeric, consisting of -, - and γ-subunits, and serve to stimulate or repress the activity of multiple cellular effector enzymes (Gilman, 19 87) Some 16 distinct G protein α-subunits define major categories of cell responses; for example, stimulatory (Gs) and inhibitory (Gi) G proteins activate or repress,... transcription factor FAST -1 was the first of these interacting proteins to be identified, but it is likely that the Smads target many transcriptional regulatory proteins Smads 6 and 7 are known as inhibitory Smads, and they act to inhibit the activation of the R-Smads by binding to the type I receptor Smads 6 and 7 are up-regulated by BMP and TGF-β pathway signaling, respectively, and are likely part of a negative... effector sys- 2 GENERAL ASPECTS OF RECEPTOR ACTION 2 .1 Receptors as Mediators of Endocrine Signals The concept that hormone action is mediated by receptors is most often attributed to the work of Langley on the actions of nicotine and curare on the neuromus- From: Endocrinology: Basic and Clinical Principles, Second Edition (S Melmed and P M Conn, eds.) © Humana Press Inc., Totowa, NJ 9 10 cular junction... Smad proteins they activate; (B) mechanisms of ligand binding to receptors for the two major subclasses of TGF-β ligands, TGF-β class and BMP class; (C) example of generic signaling through the Smad pathway, although this example of ligand binding illustrates initial binding to type II receptor, which is characteristic of TGF-β class high-affinity ligand-binding determinant Binding of hormone allows the... Interdepartmental Clinical Pharma-cology Center, UCLA School of Medicine, Los Angeles, CA RUN YU, MD, PhD • Division of Endocrinology, CedarsSinai Medical Center, UCLA School of Medicine, Los Angeles, CA IRINA V ZHDANOVA, MD, PhD • Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA Value-Added eBook/PDA on CD-ROM This book is accompanied by a value-added CD-ROM that . references and index. ISBN 1- 5 882 9-4 2 7-7 (alk. paper) eISBN 1- 5 925 9-8 2 9-3 1. Endocrinology. 2. Hormones. 3. Endocrine glands—Diseases. I. Melmed, Shlomo. II. Conn, P. Michael. QP187.E555 2005 612 .4—dc22. Service is: [ 1- 5 882 9-4 2 7-7 /05 $30]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging-in-Publication Data Endocrinology : basic and clinical principles. 612 .4—dc22 2004 018 638 v Endocrinology: Basic and Clinical Principles, Sec- ond Edition aims to provide a comprehensive knowl- edge base for the applied and clinical science of endocrinology. The