Vertebrate Endocrinology FOURTHEDITION This page intentionally left blank Vertebrate Endocrinology F O U R T H E D I T I O N David O. Norris AMSTERDAM•BOSTON•HEIDELBERG•LONDON NEWYORK•OXFORD•PARIS•SANDIEGO SANFRANCISCO•SINGAPORE•SYDNEY•TOKYO AcademicPressisanimprintofElsevier ElsevierAcademicPress 30CorporateDrive,Suite400,Burlington,MA01803,USA 525BStreet,Suite1900,SanDiego,CA92101-4495,USA 84Theobald’sRoad,LondonWC1X8RR,UK Thisbookisprintedonacid-freepaper.(cid:2)(cid:3) Copyright©2007,ElsevierInc.Allrightsreserved. Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans, electronicormechanical,includingphotocopy,recording,oranyinformation storageandretrievalsystem,withoutpermissioninwritingfromthepublisher. PermissionsmaybesoughtdirectlyfromElsevier’sScience&TechnologyRights DepartmentinOxford,UK:phone:(cid:2)+44(cid:3)1865843830,fax:(cid:2)+44(cid:3)1865853333, E-mail:[email protected] viatheElsevierhomepage(http://elsevier.com),byselecting“CustomerSupport” andthen“ObtainingPermissions.” LibraryofCongressCataloging-in-PublicationData Norris,DavidO. Vertebrateendocrinology/author,DavidO.Norris.—4thed. p. cm. Includesindex. ISBN-13:978-0-12-088768-2(alk.paper) ISBN-10:0-12-088768-1(alk.paper) 1. Vertebrates—Endocrinology. I. Title. QP187.N672007 596(cid:4).0142—dc22 2006020110 BritishLibraryCataloguinginPublicationData AcataloguerecordforthisbookisavailablefromtheBritishLibrary. ISBN13:978-0-12-088768-2 ISBN10:0-12-088768-1 ForallinformationonallElsevierAcademicPresspublications visitourWebsiteatwww.books.elsevier.com. PrintedintheUnitedStatesofAmerica 07 08 09 10 9 8 7 6 5 4 3 2 1 Working together to grow libraries in developing countries www.elsevier.com | www.bookaid.org | www.sabre.org This book is dedicated to my family (spouse Kay and daughters Sara Engel and Linda Quintana) who have supported me even when I haven’t deserved it, and to the hundreds of bright, inquiring students at the UniversityofColoradothathavemadethelast40yearsofteachingandresearchinvertebrateendocrinology a thorough delight. This page intentionally left blank CONTENTS Preface viii 1. An Overview of Chemical Bioregulation in Vertebrates 1 2. Methods to Study Bioregulation 30 3. Synthesis, Metabolism, and Actions of Bioregulators 46 4. Organization of the Mammalian Hypothalamus-Pituitary Axes 106 5. The Hypothalamus-Pituitary System in Non-Mammalian Vertebrates 168 6. The Hypothalamus-Pituitary-Thyroid (HPT) Axis of Mammals 221 7. The Hypothalamus-Pituitary-Thyroid (HPT) Axis of Non-Mammalian Vertebrates 244 8. The Mammalian Adrenal Glands: Cortical and Chromaffin Cells 272 9. Comparative Aspects of Vertebrate Adrenals 298 10. The Endocrinology of Mammalian Reproduction 322 11. Comparative Aspects of Vertebrate Reproduction 371 12. Bioregulation of Feeding, Digestion, and Metabolism 427 13. Comparative Aspects of Feeding, Digestion, and Metabolism 470 14. Bioregulation of Calcium and Phosphate Homeostasis 486 Appendix A. Abbreviations of Endocrine Terms 512 Appendix B. Vertebrate Tissue Types 519 Appendix C. Amino Acids and Their Symbols 522 Appendix D. Bioassays 523 Index 531 vii PREFACE TO THE FOURTH EDITION Vertebrate Endocrinology has evolved into a 4th edition that has incorporated new information and insights gained by this author during a fourth decade of teaching and research within the field of endocrinology. It represents a virtual rewrite and reorganization with the addition of many new chemical bioregulators as well as new understandings of the synthesis, actions, and metabolism of former bioregulators. Included are new insights into the evolution of these systems. Furthermore, the old distinction of separate regulatory systems (e.g., nervous, endocrine, immune, paracrine) has becomesoblurredduringthepastdecadethatwenowmustconsideranorganismtobeanintegrated playingfieldforchemicalbioregulatorsproducedinavarietyofmannersbyagreatvarietyoftissues and organs with a considerable amount of cross-talk. Perhaps, even the title of this edition should have been altered to simply The Chemical Bioregulation of Vertebrate Physiology and Behavior to reflect this change of emphasis from endocrinology sensu stricto. I hope this new edition will continue the tradition of introducing undergraduate and graduate students to the exciting, complicated, and integrative field of “endocrinology” that is more broadly interpreted in this edition as “chemical bioregulation.” Whether interested in clinical, evolutionary, and/or environmental aspects of endocrinology, it is my intention that students receive a broad exposure in this book that will enable them to become self-learners by providing a background to the primary literature. Although tremendous gains in molecular techniques since the 3rd edition have allowed creative scientists to greatly increase our understandings of the intricate interrelatedness among chemical bioregulatory mechanisms and their evolution, perhaps the most important changes have been the recognitionanddocumentationofendocrinedisruptionbychemicalsintheenvironment.Theseenvi- ronmentally endocrine active chemicals (EACs) are capable of disrupting normal life history events including development, sexual differentiation, and post-embryonic functions such as metabolism, stress responses, sexual maturation, reproduction, and behavior. The possible clinical implications of these EACs for present human populations are of immediate concern, and there is mounting evidence of their potential impacts on future generations. Some of these EACs have appeared in the environment simply through careless and/or thoughtless behavior related to our obsessions for “betterlivingthroughchemistry”andfor“economicgain”regardlessofthecosttotheenvironment. Other EACs are the consequence of the burgeoning size of the human population, its concentra- tions into cities, and its reliance on artificially maintained agriculture and animal husbandry. EACs include pesticides, herbicides, antibiotics, fertilizers, and industrial products (e.g., PCBs, dioxins, and plasticizers) as well as ingredients of household products such as detergents, shampoos, and cosmetics.Furthermore,highdensitiesofhumansanddomesticanimalshaveresultedintheaddition of biologically relevant concentrations of reproductively active hormones and pharmaceuticals to aquaticenvironmentsthroughwastewatereffluentsandapplicationofbiosolidstoagriculturalfields. Of greatest long-term (evolutionary) concern perhaps may be the effects of thyroid inhibitors on central nervous system development and the effects of estrogenic and androgenic EACs on sexual viii Preface ix differentiation (sex reversal and intersex production) of embryos and immature animals as well as the induction of estrogen-based cancers and contraception in adults and future generations. The widespread use of pharmaceuticals, especially in the “developed” countries, is resulting in the pres- ence of biologically relevant quantities of these drugs in water supplies and even in drinking water. Among these drugs are estrogenic birth control ingredients, (cid:4)-blockers used for blood pressure control or cardiac therapy, selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (i.e., Prozac®(cid:3), and plasma cholesterol-lowering compounds, to name a few. The widespread contami- nation of natural environments means that it is no longer possible to study animals under natural conditions.Hence,fieldstudiesmustrelyonreferencepopulationslackingonlythebioregulatorthey wishtostudyratherthancontrolpopulationssinceallanimalsinnatureareexposedtosomeEACs. And the ultimate impacts of EACs on microorganisms, plants, and invertebrate populations and theirimplicationsfornaturalecosystemsmaybeevenmoreimportantthanthoseonvertebrates.Itis myhopethatstudentswhounderstandtheintricaciesandinterrelatednessofchemicalbioregulatory systems such as described in this text will be best prepared to deal with the threat of environmental EACs in the future. If left unchecked, EACs could lead to the destruction of natural ecosystems as we know them. ACKNOWLEDGEMENTS This book is in part a product of my need to teach the excitement of discovery in the biological sciences that was instilled in me by my undergraduate advisor and botany professor at Baldwin- Wallace College, Dr. Donald S. Dean. Were I to attempt to name all of the endocrine people who have contributed directly or indirectly to this edition, I would undoubtedly overlook many of them. I can acknowledge the vast majority, however, by simply referring to the many direct academic descendents and postdoctoral students of my past mentors in vertebrate endocrinology: Aubrey Gorbman, Howard Bern, and Donald Farner as well their many academic sons and daughters, grandsonsandgrand-daughters,great-grandsonsandgreat-grand-daughters,etc.Thesedescendents continue to add to our understanding of vertebrate endocrinology through teaching and research. My own understanding of chemical bioregulation has been strongly influenced by my many years of interactions with colleagues Dr. Richard Evan Jones and more recently Dr. Pei-San Tsai, as well as with the many undergraduate and graduate students in vertebrate endocrinology we have trained inourlaboratoriesattheUniversityofColoradoinBoulder.Questions,challenges,andindependent interpretations of the literature by these students have strongly affected my thinking about chemical bioregulation over the years to the extent that I can no longer honestly separate their ideas from my own. Among those former graduate students are Dr. Harriet B. Austin Dr. James A. Carr Dr. Laura M. Carruth Dr. Rubai Ding Dr. David Duvall Dr. Kevin T. Fitzgerald Dr. William A. Gern Dr. John C. Gill Dr. Louis P. Guillette, Jr. Dr. Earl T. Larson