The elucidation of the structure, function, and clinical significance of the neurohypophysis has been one of the most rewarding chapters in the history of endocrinology. Diabetes insipidus, which can be manifested by passage of 15 liters of urine a day, is one of the most dramatic disorders of the endocrine system, and can readily be managed by replacement therapy with the natural secretions of this gland, or with synthetic analogues that provide a more favorable therapeutic ratio. The neurohypophysis is the archetypical neurosecretory gland. Its secretions arise within well defined nerve cells in the hypothalamus, are transported by axoplasmic flow to nerve endings in the neural lobe, are released in response to propagated action potentials, and are regulated by neurotransmitters and osmotic signals. This gland is a model for homeostatic regulation; functional disorders of this regulation lead to well defined disorders such as the syndrome of inappropriate secretion of antidi uretic hormone (SIADH), which can be mimicked by the ectopic secretion of its hormones by tumor cells. These hormones were the first peptides to be sequenced and synthesized chemically and their structure-function relations have been characterized as well as those of any of the peptide hormones. The concept that peptide hormones generally arise as products of the processing of a larger prohormone precursor was first developed from studies of the neurohypophysis. The concept of stimulus-secretion coupling was first ap plied in neuronal tissue to the neurohypophysis.

I consider it an honor to have been asked to write the Foreword for The Diabetic Pancreas. Although I have been involved in the study of the pancreas since 1921, my interest goes back even further to the time, in 1918, that my father's sister, a nurse who had trained at the Massachusetts General Hospit.al, devel oped diabetes, lost weight, and died in diabetic coma. This sad event made a deep impression on me and was certainly pardy responsible for my choosing to join the Department of Physiology of the University of Toronto to begin a career in research into diabetes. This is not the place to describe in detail the wide-ranging research and study of the diabetic pancreas in which I have engaged in the past 56 years. Suffice it to say that I am familiar enough with the subject area to be able to predict a great future for this book. The editors have undertaken a very ambitious and worthwhile project, and their efforts have been supported and strengthened by contributors who are respected authorities in their fields, thus ensuring a successful presentation of this major work."

Despite a new title, Contemporary Metabolism, Volume 1 is actually the third volume in a continuing series and succeeds The Year in Metabolism 1975- 1976 and The Year in Metabolism 1977. As in the earlier volumes, the same internationally recognized authorities review the noteworthy recent devel opments in their areas of expertise. In many instances they also address aspects that have not been considered previously. In this volume, Dr. J. Edwin Seegmiller again updates progress in understanding disorders of purine and pyrimidine metabolism. However, particular emphasis is placed on the emerging relationships with immune mechanisms. Dr. Charles S. Lieber is joined by Dr. Enrique Baraona in a continuing review of metabolic actions of ethanol. This chapter examines effects of ethanol on protein metabolism and selected features of lipid metabolism-two areas that were not included in the earlier volumes. Dr. DeWitt S. Goodman's review of disorders oflipid and lipoprotein metabo lism builds on his previous chapters, but much additional attention is directed to a critical analysis of recent advances in epidemiology and lipoprotein structures. In collaboration with Dr. Brian L. G. Morgan, Dr. Myron Winick devotes his entire chapter to a detailed review of the impact of nutrition upon brain development-an overview that has now been rendered possible by the burgeoning recent developments in this area."

This volume in the series Developments in Medical Virology deals with viruses involved in diabetes mellitus, a syndrome with a strong genetic background that causes damage to the regulation of insulin synthesis and function. Viruses were found either to cause or to stimulate diabetes mellitus in man and in animal models. The nature of the role of viruses is described by many of the scientists who participated in the original studies. To complete the picture, chapters were included that deal with the insulin gene, the secondary structure of the proinsulin and insulin receptor polypeptides, pancreatic Langerhans islets, and clinical considerations of the disease. The aim of Developments in Medical Virology is to elucidate processes involving viruses as pathogens of cells and organisms, with special attention to human diseases. A number of volumes will be devoted to viruses affecting specific organs (e.g. brain, liver, etc.), while others will elaborate on the clinical experience in the use of antiviral drugs. The series is published in parallel with Developments in Molecular Virology, designed to present an analysis of molecular mechanisms implicated in virus infection and replicative processes. In addition, the series Developments in Veterinary Virology provides information on viruses causing diseases in animals, with special emphasis on aspects of interest to veterinarians.

Bilateral Communication Between the Endocrine and Immune Systems, "Volume 7" in the Springer-Verlag "Endocrinology and " "Metabolism" Series, offers the most current information and recent advances in the area of communication and regulation between the Immune and Endocrine Systems. Immune-Endocrine Interactions are reported to play pivotal roles in both activation and down-regulation of immune responses and this volume provides the most up-to-date research and findings on the immune-endocrine relationship. The contributing authors are internationally recognized experts in this area and have written chapters on such diverse topics as Interactions between the Pituitary and Immune Systems, Effects of Estrogens and Androgens on Immune Response, The Role of Sex Steroids in Immune System Regulation, and Neuroendocrine and Thymus Interactions During Development and Aging. This volume is a must for all endocrinologists and endocrinology residents.

Behavioral medicine has blossomed as an area of systematic investiga tion during the past 10-20 years. Throughout its steady growth, there have been increasing interest and specialization in the study of neuro psychological and behavioral aspects of diabetes. This book attempts to capture and report exciting new developments in the study of both insulin-dependent (Type I) and non-insulin-dependent (Type II) dia betes mellitus. Accordingly, it is divided into two major sections. Physiological aspects of each disease, which differ significantly in pathophysiology and course, are discussed in separate medical over views that introduce each major section. These overviews are written by Drs. Tsalikian and Zimmerman, leading medical researchers in insulin and non-insulin-dependent diabetes, respectively. Each section also contains chapters describing neuropsychological and cognitive disease correlates, psychosocial patterns of adjustment, and treatment adher ence issues. Psychological aspects of insulin-dependent diabetes have been studied more extensively than non-insulin-dependent diabetes, perhaps because it is more often associated with graver medical compli cations. Therefore, there is a larger body of research to review and the first section has been divided into chapters on cognitive disease se quelae in populations of children and adults, separately. In his chapter, Dr. Ryan discusses developmental factors related to the unique sensi tivity of the brain to metabolic derangement. Dr. Holmes reviews studies of adults with diabetes and the cognitive correlates of both acute and chronic blood glucose disruption. Developmental disease is sues are further covered in Dr."

This book addresses diabetes controversies, specifically in the management of etiology and the disease itself. Chapters also examine the complications associated with diabetes. The volume covers commonly accepted forms of therapies and complications, as well as new and emerging advances and therapies and inadequacies in several standard treatments. Comprehensive and timely, this book is an essential reference for those treating and researching diabetes.

A panel of leading experts integrate the latest findings from basic and clinical science to create a comprehensive treatment of the processes by which the brain acts as an endocrine organ, not only to control hormonal functions, but also to maintain homeostasis and regulate behavior. The authors-recognized both as leaders in their fields and as skilled teachers-provide systematic coverage of the analytical, anatomical, functional, clinical, and pathological aspects of neuroendocrinology. Topics range from the interactions between the nervous and endocrine systems to the regulation of reproduction, development, metabolism, fluid balance, and biological rhythms. Neuroendocrinology in Physiology and Medicine offers an unprecedented marriage of clinical and basic knowledge that has been missing from classical neuroscience, endocrinology, and physiology texts. It will teach today's medical students and serve researchers as a valuable reference to this rapidly growing field.

In the past five years, so much additional progress has been made in ourunderstanding of both the basic and c1inical aspects of a wide variety of thyroid disorders that a second edition of Diseases of the Thyroid was considered a necessary addition to the Contem porary Endocrinology series. Fresh perspectives also seemed warranted, so we recruited new authors for many of the chapters and believe that this edition will provide the reader with further insights into the pathophysiology and c1inical presentation and treatment of thyroid disease. It inc1udes topics ranging from neonatal thyroid screening, thyroid dysfunction during infancy and childhood, peripartum thyroid disorders, thyroid disease in the elderly, and the c1inical relevance of the sodiurnliodide symporter (NIS) to the pathogenesis and treatment of nodular goiter, thyroid cancer, thyrotoxicosis, and hypothyroidism. The worldwide problem of iodine deficiency and its eradication is also discussed, along with environmental goitrogens and iodine-induced thyroid disease. I am indebted to all the contributors for their cooperation and expertise in providing their chapters in an extremely timely fashion, to Mr. Thomas Moore and Mr. Craig Adams from Humana Press for their expert assistance, and to Ms. Christine Archung for providing superb administrative assistance. Lewis E. Braverman, MD v CONTENTS Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Molecular Mechanisms of Nuclear Thyroid Hormone Action William W. Chin and Paul M. Yen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 Nongenomic Actions of Thyroid Hormone Paul 1. Davis and F aith B. Davis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 3 Thyroid Testing: A Clinical Approach Laurie A. Kane and Hossein Gharib . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

This volume includes the latest diagnostic criteria for PCOS and comprises the most up-to-date information about the genetic features and pathogenesis of PCOS. It critically reviews the methodological approaches and the evidence for various PCOS susceptibility genes. The book also discusses additional familial phenotypes of PCOS and their potential genetic basis. All four editors of this title are extremely prominent in the field of PCOS.

Diabetes affects an estimated 20 million people in the United States, with many people remaining unaware that they suffer from the disease. While the number of diabetics continues to rise, the number of caregivers who specialize in diabetes treatment does not. In Educating Your Patient with Diabetes, Katie Weinger and Catherine Carver assemble commentary from a panel of leading diabetes practitioners and researchers and put together a highly readable guide to supplying patients with diabetes with the information and ability to successfully cope with their disease. The authors and editors provide substantive data on successful models of diabetes education and the process of educating diabetes sufferers. Additional chapters discuss diabetes in pregnancy, the challenge of weight and diabetes management in clinical practice, and diabetes education in geriatric populations. Timely and accessible, Educating Your Patient with Diabetes is a must have for all diabetes educators, physician assistants, nurses, and endocrinologists who endeavor to support their patients' diabetes self-care efforts and help them maximize the opportunities for patient learning.

During the past five to ten years, a variety of tools has been developed in the disciplines of both gene engineering, and molecular and structural biology. Some of these advances have permitted scientists not only to identify and characterize genes, but also to target these genes by disruption, thus eliminating their function in living animals, and to det- mine the biological responses to altered gene products. This has particular significance in endocrine systems, in which feedback mechanisms between the hypothalamus, pi- itary, and end organs are critical in normal physiology. Interpretation of the physiological significance, or the site of action of specific molecules in this context, has been difficult prior to transgenic technology. Major advances have occurred specifically in the areas of growth and development, and of reproduction. Coupled with analysis of naturally occurring mutations in humans, the use of transgenic animals and in vitro systems has recently allowed endocrinologists to understand the importance of specific thyroid hormone receptor isoforms in vivo, the molecular basis for generalized resistance to thyroid hormones via mutations in the nuclear receptor, and mechanisms for suppressing gene transcription. Previously designated "orphan rec- tors," such as steroidogenic factor-1, were demonstrated to have critical roles in dev- opment and reproduction. Other nuclear receptors-including those for thyroid hormone, estrogens, androgens, and progesterone-were shown to bind to coactivator and co- pressor proteins that modified their transcriptional activity, and contributed to the ce- specific effects of the hormones.

Distinguished clinician-scientists describe in concise studies their most difficult cases and reveal what they did, how they did it, and why. The cases cover a wide range of endocrine problems. Each case study reviews how the patient was managed, details the reasons why various tests and treatments-many only recently available-were carried out, and provides references to ensure that those novel methodologies can be easily translated into the endocrine specialist's daily practice. The authors provide practical solutions for these difficult-to-manage cases, and successfully apply knowledge fresh from the laboratory to decisions about patient management. Practical and stimulating, Challenging Cases in Endocrinology demonstrates for every clinical endocrinologist precisely how specialists approach their most challenging cases and how these approaches can be effectively applied in the daily practice of endocrinology.

RNA binding proteins are an exciting area of research in gene regulation. A multitude of RNA-protein interactions are used to regulate gene expression including pre-mRNA splicing, polyadenylation, editing, transport, cytoplasmic targeting, translation and mRNA turnover. In addition to these post-transcriptional processes, RNA-protein interactions play a key role in transcription as illustrated by the life cycle of retroviruses. Unlike DNA, the structure of RNA is highly variable and conformationally flexible, thus creating a number of unique binding sites and the potential for complex regulation by RNA binding proteins. Although there is a wide range of topics included in this volume, general themes have been repeated, highlighting the overall integrative nature of RNA binding proteins. The chapters have been separated into three different sections: Translational Control; mRNA Metabolism; and Hormonal and Homeostatic Regulation. The chapters of this volume were written with the seasoned investigator and student in mind. Summaries of key concepts are reviewed within each chapter as well as guiding questions that can be used to stimulate class discussions. The Editors of this volume hope that this compendium educates, enthralls, and stimulates the readers to look to the future possibilities in this rapidly evolving field.

The explosive growth in the field of molecular biology over the last two decades has started to make a great impact on clinical medicine. Genes have been cloned for diseases that were poorly understood only a decade ago. Additionally, investigators are increasingly aware that there are strong genetic components to complex disorders, such as osteoporosis, that are not classically thought of as genetic disorders. New insights into the pathogenesis of metabolic bone diseases have been obtained from investigations into the molecular biology of these diseases and new therapies will become available based on these new insights. In The Genefies of Osteoporosis and Metabolie Bane Disease, I have assembled an internationally renowned group of experts to write the various chapters. Each of the authors is an expert in his/her field who is currently performing research on the content of their chapter and have made important contributions to the understanding of the clinical fea tures and pathophysiology of metabolic bone disease and genetics. The first part of The Genefies of Osteoporosis and Metabolie Bane Disease addresses issues related to genetic contributions to the development of osteoporosis and the many factors that must be considered when searching for genesthat predispose to osteoporosis. The second sec tion addresses recent advances in the clinical and molecular biological aspects of inherited metabolic bone disorders. The last section reviews the latest techniques for finding genes that predispose to metabolic bone diseases.

Authoritative researchers and clinicians review our latest understanding of andrology in both basic science and clinical medicine. Topics range from explaining the biology of androgens-from several different perspectives-to illuminating their role in the development and modulation of physiologic systems. Authors demonstrate in a number of cases that testosterone can be a useful adjunct to the treatment of a variety of disease states. Other chapters consider important topics such as androgens use in athletes, the potential of androgens to improve physical function and quality of life in older men, and androgens as potential male contraceptives.

It has been over 40 years since the original report by Salmon and Daughaday demon strating that the ability of GH to stimulate sulfation of cartilage was mediated by a "sulfation factor. " In the ensuing decades, it has become apparent that this "sulfation factor activity" encompasses a complex system ofligands (IGFs), receptors, and carrier proteins that are, in tum, responsible for a wide array of cellular actions. The IGF system has been demonstrated to be critically involved in both intrauterine and postnatal growth, and to have important implications in cancer biology as well, owing to the ability of the IGFs to function in endocrine, paracrine, and autocrine modes and given the wide distri bution of IGFs in virtually every organ system. The contributions to The /GF System reflect the wide span of interest in the IGF system and its implications for normal and abnormal growth and metabolism. The chapters have been divided into four broad sections: I. Molecular biology of the IGF system; II. Bio logical actions of the IGFs; III. IGF physiology; and IV. Clinical aspects of the IGFs. We have made every effort to highlight the major contemporary themes in IGF biology, but as is inevitable in such a fast-moving field, perspectives will continue to change as new information is accumulated."

Gerald Reaven, the discoverer of Syndrome X, and a panel of world-class investigators thoughtfully summarize our current understanding of how insulin resistance and its compensating hyperinsulinemia play a major role in the pathogenesis and clinical course of high blood pressure and cardiovascular disease-the so-called diseases of Western civilization. These distinguished authorities detail, for the first time, the pathophysiological consequences and the clinical syndromes, excluding Type 2 diabetes, related to insulin resistance. They also examine the genetic and lifestyle factors that contribute to the wide differences in insulin action that exist in the population at large. Timely and authoritative, Insulin Resistance: The Metabolic Syndrome X illuminates the full importance of insulin resistance as a major cause of hypertension, heart disease, and polycystic ovary syndrome.

Don P. Wolf and Mary Zelinski-Wooten provide a comprehensive review of the procedures and techniques used in assisted reproduction, as well as in nuclear transfer for both the treatment of human infertility and the propagation of animals. Combining the details of clinical application with the physiological facts of reproduction, the authors treat subjects such as the in vitro maturation of oocytes, embryo culture, intracytoplasmic sperm injection, and the process of nuclear transfer. Cutting-edge and wide-ranging, Assisted Fertilization and Nuclear Transfer in Mammals offers clinical ARTs practitioners, research scientists, those responsible for animal care, and students not only an informative historical perspective on the development of ARTs, but also updates on several of the more dynamic clinical areas, and a highly practical understanding of their applications.

Leading researchers and experienced clinicians join forces not only to illuminate today's understanding of the endocrinology of menopause, but also to provide a sound basis for its successful management. These seasoned experts review in detail the cardiovascular, bone, brain, and genitourinary changes that accompany menopause and spell out the risks, benefits, and alternatives of conventional hormone replacement therapy. Selective estrogen receptor modulators (SERMs), androgen replacement, calcium supplementation, and the role of phytoestrogens are also fully reviewed. Menopause: Endocrinology and Management offers practicing physicians a comprehensive understanding of the menopause process, as well as an evidence-based approach to optimizing treatment strategies for the challenging medical problems accompanying this important period in women's lives.

Diabetes mellitus is the collective name for a group of diseases associated with hyperglycemia (high levels of blood glucose) caused by defects in insulin p- duction, insulin action, or both. About 6. 2% of the US population (17 million people) have diabetes mellitus. It is the leading cause of kidney failure, bli- ness, and amputations. It is also a major risk factor for heart diseases, stroke, and birth defects. Diabetes Mellitus: Methods and Protocols provides a state-of-the-art account of the experimental methodology for studying the molecular defects leading to diabetes mellitus, both at the molecular and biochemical levels. The chapters cover a wide range of topics written by experts in their respective fields and are organized in two sections: Insulin Production and Insulin Action. The detailed experimental protocols presented, including the notes of interest, provide a very useful tool for basic researchers and clinicians for investigating and treating this disease. Each chapter starts with an introduction to a specific technique and explains its application in the field of diabetes research. Following the list of materials, a detailed description of the technique is presented in the methods section in a way that enables the successful execution of the protocol. The "Notes" section at the end discusses the pitfalls of the technique and alternative approaches. I am grateful to the numerous scientists who have contributed to this volume by writing both highly detailed and understandable chapters.

The aim of this book is to inform clinicians of recent advances in obesity research and provide a review of current treatment issues and strategies. Part 1 covers new discoveries in the physiological control of body weight, as well as the pathophysiology of obesity. Part 2 covers a range of issues that are central to the clinical management of obese patients. This illustrated volume will stimulate and engage clinicians.

An unprecedented compilation of state-of-the-art advances in clinical research by premier clinical scientists around the world. This volume discusses the methods of clinical research and the interpretation of their results in studies of normal individuals, obese subjects, and patients with diabetes mellitus. Along the way, the authoritative contributors writing here illuminate how changes in the hormone action and substrate metabolism of healthy humans may lead to obesity and noninsulin-dependent diabetes mellitus.

This book covers the most important clinical and bench science aspects of metabolic syndrome. It will be of value to all of those seeking a comprehensive update on the metabolic syndrome. Furthermore, it will provide a broad basis for advancing research in the multiple intersecting disciplines encompassed by the metabolic syndrome.

During the past several decades, much research effort has gone into the elucidation of the role of neuroendocrine systems as secretory and metabolic regulators of cells of a variety of organs and structures, including the testes, ovaries, adrenals, thyroid, pituitary gland, and mammary glands. However, the role of cells comprising such organs and structures in the modulation of neuroendocrine processes has received considerably less is generally less well appreciated. attention and Nonetheless, it is important that we understand the actions on neuroendocrine systems of substances that reach the brain by way of the vasculature, including hormones, cytokines, toxins, amino acids, drugs, and similar agents. In order to analyze the present state of knowledge on this topic, experimental scientists and clinicians, whose shared interests include actions of circulating agents on the brain, met at a satellite symposium of the XXXI International Congress of Physiological Sciences. This symposium, entitled Circulating Regulatory Factors and Neuroendocrine Function, was held in Smolenice Castle, Czechoslovakia, June 26-July 1, 1989, and reviews delivered at this symposium as invited presentations are published in this volume. Presentations given as free communications have been published separately and are available in Endocrinologia Experimentalis 24: 1-273, 1990.