THIS BOOK collects together papers given at a NATO Advanced Research Workshop held at Il Ciocco (Lucca), Italy, from the 9th to the 15th April, 1989. It sets out to present the current state of understanding of the principles governing the way fluxes and concentrations are maintained and controlled in metabolic systems. Although this is a topic that has held the interest of biochemists for many years, it is only quite recently that the methods of analysing the kinetics of multi-enzyme pathways developed over the past two decades have come to be widely discussed or applied experimentally. Many biochemists remain sceptical that the new methods offer a real advance (except in complexity) over the landmark discoveries of the 1950s and 1960s relating to inhibition of enzymes at branch-points by the end products of metabolic pathways, and the interpretation of allosteric effects and cooperativity. Even those who have become convinced that the classical ideas provide only the starting point for understanding metabolic control have been by no means unanimous in their assess ment of the direction in which one should advance. In this book we have tried to include all of the current points of view, including the view that the classical theories tell us all that we need to know. We have not seen it as our role as editors to paper over the cracks that exist and to pretend that we can speak to the world with one voice."

Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology."

The disorders induced by iodine deficiency affect at least one billion people. Because ofits effects on brain development, iodinedeficiency is the single most preventable cause of mental retardation in the world. Therefore, the United Nations and the Heads of State of almost all the world's countries represented at the Summit for Children in 1990 adopted resolutions to eradicate the disorders induced by iodine deficiency (IDD) by the year 2000. For geological and socio-economic reasons, most of the populations affected by iodine deficiency disorders live in isolated and usually mountainous areas, in pre industrialized parts ofthe world. The problem of iodine deficiency in Europe has been greatly underestimated in the last decades. After the remarkable studies on the effects of iodine deficiency and their prevention and correction in Switzerland, IDD was generally considered no longer a significant public health problem in Europe. However, surveys carried out in the early 1980's under the auspices of the European Thyroid Association, clearly demonstrated the persistence of moderately or even severely affected areas. These surveys also highlighted the lack ofinformation about large parts ofEurope, especially its eastern part. It is only quite recently, following major changes in international relations and thanks to the support of UNICEF, WHO, the International Council for the Control of Iodine Deficiency Disorders and the European Thyroid Association, that more extensive surveys have been conducted in several parts of Europe hitherto almost unexplored. These surveys showed that most European countries were iodine deficient."

It has been ten years since the National Hormone and Pituitary Program (then called the National Pituitary Agency) sponsored a symposium on human growth hormone (hGH). Numerous advances have occurred during this period. This book does not attempt to summarize past achievements. Rather, it deals with the contemporary issues in hGH research. A discussion of the present state of the art, of necessity, includes a review of the past. Some of the topics herein discussed include the following: 1. Growth hormone releasing factor (GRF). In 1973, the growth hormone inhibitory factor (somatostatin) had recently been discovered. The search for a releasing factor in humans led to its discovery not in the pituitary but in a pancreatic tumor that secreted growth hormone. The advances are discussed in this book. The current hope is that GRF will eventually become an effective therapeutic agent for idiopathic hypopituitarism in childhood and adolescence. 2. Biosynthesis of hGR by recombinant DNA technology. Current advances are discussed. Although hGH is not yet an approved drug, it will eventually become one. This will broaden our horizons in terms of hGH effectiveness in disorders other than hypopituitary dwarfism. The current experience with this type of hGH in both the Vnited States and Europe is reviewed by several authors.

Diabetic nephropathy is a tragic illness. Its often insidious onset in the insulin dependent (type I) diabetic, typically a young adult, heralds the last act in the course of a disease that will increasingly become the dominant preoccupation in the patient's shortened life. For most type II diabetics, the beginning of clinical renal insufficiency is but a phase in a continuous deterioration that affects the integrity ofjob, marriage, and family. The nephropathic diabetic is hypertensive, has worsening retinopathy, and more often than not, is also plagued by peripheral vascular insufficiency, heart disease, gastrointestinal malfunction, and deepening depression. Until the 1980's, few type I diabetics who became uremic (because ofdiabetic nephropathy) lived for more than two years. Hardly any attained true rehabilitation. This dismal prognosis is changing substantially for the better. Research in diabetes has resulted in striking advances at both ends of the type I diabetic's natural history. In one exciting clinical trial now underway in London, Ontario, halfofchildhood diabetics treated with cyclosporine within six weeks of onset evince"permanent" disappearanceofhyperglycemia and the need for insulin. At the otherendofthe natural historyofdiabetes for the nephropathic patientwith worsening eye disease (renal-retinal syndrome), who receives a kidney transplant, patient and graft survival, two years after cadaveric kidney transplantation in type I diabetics is now equal to that of the nondiabetic."

Male Reproductive Function gives an up-to-date review on the physiology and disease processes associated with the male reproductive system. The first few chapters describe the regulation of the functions of the testis and the integration of its components: germ cells, Sertoli cells and Leydig cells. This is followed by a description of puberty and aging, and the disorders or dysfunction that may be associated with these physiological processes. Discussions on the current methods for the diagnosis and treatment of male hypogonadism, male infertility and male sexual dysfunction follow, with detailed descriptions of types of androgen replacement and the benefits and risks of such treatment. The book concludes with the development of male contraception and the possible influence of the environment on the male reproductive system. Male Reproductive Function represents a conglomeration of the efforts of experts in andrology from all over the world, both in basic cellular/molecular biology as well as in clinical science and practice. This book is suitable for endocrinologists, urologists, general internists, gynecologists and other students in the field of male reproduction.

Proceedings of the First International Meeting of the Pancreatic Islet Study Group held in the Alicante, Spain, November 25-28 1994

Proceedings of the Third Hans Selye Symposium on Neuroendocrinology and Stress held in Budapest, Hungary, August 17-21, 1992.

The discovery of hypothalamic factors that inhibited growth hormone secretion and of pancreatic factors that inhibited insulin secretion were the first clues to the existence of somatostatin. During the course of efforts to isolate growth hormone releasing factor, Krulich, McCann and Dhariwal found that hypothalamic extracts contained a potent inhibitor of growth hormone secretion. They postulated that growth hormone secretion was under a dual control system, one inhibitory and the other excitatory (I) . In studies being carried out at about the same time, Hellman and Lernmark found a factor in pancreatic extracts that inhibited insulin secretion (2). They postulated that islet cell function was regulated by local hormonal factors. With the isolation and chemical characterization of somatostatin by Brazeau and colleagues (3), and the availability of relatively large amounts of the synthetic peptide for research, it has been possible to demonstrate that both predictions were true. Subsequent work revealed that somatostatin, as initially isolated (somatostatin 14), was but one of several related peptides, part of a multigene family, with tissue specific processing. Many of the details of biosynthesis and genetic control have been worked out, and this molecule has served many workers as a model gut-brain peptide for detailed study. The peptides are widely distributed in tissues and exert an extraordinary range of effects on most glandular secretions, both internal and external.

In the forty years since melatonin's isolation and characterization, a large and multifaceted database has accrued. This book documents the diverse research contributions of most of the major laboratories in the field of melatonin research, as presented in a special conference to mark the 40 year anniversary of the isolation and chemical identification of this hormone. In addition, many chapters by younger scientists provide an exciting glimpse of where melatonin research is heading in the future.

In September, 1977, at a conference organized by Dr. Kenneth McKerns in Northeast Harbor, Maine, USA, I was asked by the Editorial Committee of the Biochemical Endocrinology series to investigate the possibility of organizing the next meeting in France. I proposed a subject which is in the area of my research interest, and this subject was accepted. On arriving back in France, I first looked for an appropriate place for the meeting, and the Chateau de Seillac was chosen in accordance with many objective criteria. We know that all who attended the meeting held in Seillac enjoyed this quiet and charming place in the Loire Valley. The next step was to choose some experts in the field who would contribute to the monograph and present their papers at a conference for the purpose of generating discussions. The action of the local committee, composed of Dr. A. Tixier-Vidal, Dr. Claude Kordon, and me, was crucial in this respect. The local committee proposed the program for the meeting and a list of the majority of contributors to be invited. I wish to thank Dr. Tixier-Vidal and Dr. Kordon for their invaluable assistance.

The follow-up to The Sunday Times bestseller The Diabetes Weight-loss Cookbook Katie and Giancarlo Caldesi are back to guide you through how to reverse the progress of type 2 diabetes, lose weight and bring your blood sugar down to a normal level. This new book is full of simple, delicious recipes that encourage and help you to sustain permanent lifestyle change. The Reverse Your Diabetes Cookbook is packed full of mouthwatering low-carb dishes using easy-to-source, inexpensive ingredients. With recipes to address common pitfalls, such as food on the go and take-to-work lunches, alongside fakeaways providing healthy alternatives to takeaway favourites, this is food to fill you up without fattening you up. With a foreword by pioneering GP and diabetes specialist Dr David Unwin, this life-changing book shows you how you too can prevent and reverse type 2 diabetes by adopting a low-carb way of life and choosing lifestyle medicine over lifelong medication.

"Frontiers In Thyroidology" assembles the prize lectures, symposia, and papers presented during the Ninth International Thyroid Congress in Sao Paulo, Brazil in September, 1985. This book represents the State-of the-Art in thyroid studies with its continuous expansion into the areas of immunology, molecular biology, clinical and environmental medicine. As its name also indicates, the material compiled in this volume defines important questions to be answered in basic and applied aspects of the thyroid. So, this book clearly demonstrates the rewards, excitement, and challenges posed by the thyroid gland. Once again, the thyroid gland, through its unique and important functions and implications in health and disease, has been able to congregate scientists throughout the world to communicate their findings, to share their expertise and experiences, and to strengthen their bonds of friendship and commitment to make a better world through their work. This publication consists of 309 papers in 19 different topics. The prize lectures and symposia review and update our knowledge in basic and clinical aspects of exceptional interest in the thyroid field. "Frontiers in Thyroidology" adds to a series of publications from previous interna tional thyroid meetings which includes: "Advances in Thyroid Research", London, 1960; "Current Topics in Thyroid Research", Rome, 1965; "Further Advances in Thyroid Research", Vienna, 1970; "Thyroid Research", Boston, 1975, and "Thyroid Research VIII", Sydney, 1980. We would like to express our gratitude to Mrs. P. Langford and Drs.

The aim of this book is to provide clear and concise information about the safe prescribing of insulin both subcutaneously and intravenously. It provides information on the different types of insulin, the delivery devices, side effects of insulin and, most importantly, on rational dose adjustment.

The sum of clinical problems caused by diabetic renal disease has been steadily increasing since the first edition of this book was published in 1988. The years since have seen tremendous progress in research activities. Importantly, this also includes improvement in the treatment programs to prevent end-stage renal failure. It has become clear that the diabetic kidney is extremely pressure-sensitive, responding to effective antihypertensive treatment by retarded progression of disease. Some agents may be more beneficial in this respect than others, although effective blood pressure reduction per se is crucial throughout the stages of diabetic renal disease. However, the prime cause of diabetic renal disease is related to poor metabolic control and it is now documented beyond doubt that good metabolic control is able to postpone or perhaps even prevent the development of renal disease. However, in many individuals we are not able to provide such a quality of control that will prevent complications, and therefore non-glycaemic intervention remains important.Maybe in the future non-glycaemic intervention will become the most important research area in diabetic nephropathy. Much information is now available on the exact mechanisms behind poor metabolic control and development of renal disease. It is likely that a combination of genetic predisposition and metabolic and haemodynamic abnormalities explain the progression to renal disease, seen in about 30% of diabetic individuals. Much of this development probably relates to modifiable genetic factors, such as blood pressure elevation or haemodynamic aberrations. However, mechanisms related to the response to hyperglycaemia are also of clear importance, as is the possibility that these metabolic or haemodynamic pathways may be inhibited. This volume reviews older data as well as the progress seen within the research on diabetic nephropathy over the last five years and describes the state of the art of the development.

We have witnessed a rapid development within the field of the kidney and hypertension in diabetes mellitus. A significant amount of work within the traditional areas has been published, and several new dimensions are now being developed, mostly in the experimental setting. These dimensions are discussed in several chapters of this new edition, The Kidney and Hypertension in Diabetes Mellitus, Fourth Edition. This volume endeavors to cover all aspects of renal involvement in diabetes. It is written by colleagues who are themselves active in the many fields of medical research covered in this volume: epidemiology, physiology and pathophysiology, laboratory methodology and renal pathology.

The study of the insulin-like growth factor (IGF) family has become an exciting area of investigation. Initially, this family consisted of ligands (insulin, IGF-I and IGF-m and receptors (the insulin receptor, the type I or IGF-I receptor and the type II or IGF-IYM-6-P receptor). Subsequently, it was discovered that six specific binding proteips (lGFBPs 1-6) playa major role in the actions of this growth factor family. In addition, there are now more potential receptors when one considers the possible roles of the insulin-receptor related receptor (IRR) and hybrid receptor dimers composed of insulin and IGF-I receptor (half-receptors). Another important aspect of this area of research is the realization that the IGFs are not only essential for normal growth and development but, in addition play an important role in the normal specialized function(s) of all tissues of the body, including the nervous system, skeleton, reproductive system, kidney, and the immune system, to name but a few. The development of recombi tant human IGF-I for clinical testing has been a major breakthrough for investigators. Potential uses include wound healing, reversal of catabolic states, diabetes, bone remodeling, recovery from acute renal failure and many others. will determine both its use and its potential hazards.

The Eleventh Midwest Conference on Endocrinology and Metabol ism in September 1975 brought together a number of leading invest igators in the areas of steroid, peptide, acetylcholine, and cate cholamine hormone receptor studies. This book is based upon the reports of investigations into hormone receptor biochemistry and physiology presented at the Conference as well as on the ensuing discussions. However, many of the manuscripts were written after the Conference. Because of this, the reader will find that some literature references and results of i vestigations are more up to-date than the Conference date would suggest. Perusal of this and previous volumes will attest to the high quality of this annual conference, due primarily to the efforts of the Planning Committee. We also acknowledge the superb efforts of the staff of Conferences and Short Courses for their assistance in organizing the Conference, and Mrs. Linda Bennett for expert sec retarial assistance in the typing of the book. Last, but certain ly not least, we express our appreciation to the various organiza tions that provided the necessary financial assistance. Leonard R. Forte John M. Franz David M. Klachko vii Contents The Receptor Concept: Prejudice, Prediction, and Paradox. . . . . Oscar M. Hechter Discussion. . . . . . . . . . . . . . 41 DeGroot, Hechter, Campbell, Freed, Barnawell, Morgan, Siegel Nuclear Receptors for Thyroid Hormone . 45 Leslie J. DeGroot 69 Discussion ............ ."

This 1987 ORPRC Symposium on Primate Reproductive Biology, the third in a series, marked the twenty-fifth anniversary of the Oregon Regional Primate Research Center (ORPRC). In organizing these symposia, we have emphasized the dedication of many ORPRC staff members to research with nonhuman primates as models for human reproduction. The first symposium in this series, organized by William Montagna, was held in May 1981. Appropriately for a beginning series, its topic was fetal endocrinology. The subject of this year's symposium was the primate ovary, and, as in the past, scientists from around the world, including Sweden, Scotland, England, West Germany, and India met in Beaverton, Oregon, to exchange ideas and information on this important "aspect of reproduction. The international scope of the symposium reflects our belief that both the problems and their solutions extend beyond national boundaries. Many of the nonhuman primates that we rely on as models are endangered as civilization, through population pressure, encroaches on their natural habitats. Without a deeper understanding of how primate reproduction is regulated, and without the control over human population that such an understanding can bring, the quality of life for all primate species may well become substantially diminished. Consequently, we dedicate these symposia to the thesis that a deeper understanding of primate reproductive biology will ultimately improve all primate life. Robert M. Brenner Charles H. Phoenix vii PREFACE Today there is renewed interest in the processes controlling the gametogenic and endocrine functions of the ovary.

Those who are familiar with the two volumes of The Year in Endocrinology may, at first glance, fail to recognize their relationship to the present volume, Contemporary Endocrinology. The name is different and the cover design different, but nonetheless the admonition against judging a book by its cover is very well taken in this instance. In fact, Contemporary Endocrinology is not only the direct linear descendant of The Year in Endocrinology, it is a purposeful clone thereof-the topics are unchanged, the talented group of authors is unchanged, and most importantly, both the objective of the work and the manner in which that objective is approached are unchanged. The objective is, of course, to assist the reader in maintaining currency with respect to important developments, both basic and clinical, in the major areas of endocrinology. We are all much too familiar, unfortunately, with the difficulty of maintaining currency these days. Our approach to dealing with the informational inflation that we are suffering is similar to that used by economists in dealing with monetary inflation, that is, to increase interest. This we have attempted to do by providing for the reader an easy-to-read group of essays in which advances in individual areas of endocrinology are re viewed broadly, synthesized, and placed into perspective by a group of authors who are authorities in their individual fields. They serve, not as guest artists, but as members of a stable Editorial Board that provides continuity by contributing to successive volumes."

Since 1948, the date of publication of Hormones and Behavior by Dr. Frank Beach, this hybrid area has received a great deal of attention from scientists representing various allied fields. As a result, the data and publications dealing with hormones and be havior have increased geometrically and on an annual basis. More recently, a number of review articles and short volumes dealing with aspects of hormones and behavior have been published. How ever, there seemed to be an overwhelming need for a synopsis of the major topics in a unified and integrated form. Thus, the reason for this edition. In these two volumes, we hope we have presented a critical assessment of the various interrelated areas dealing with hormones and behavior. In some instances, we have minimized the presenta tion of certain aspects of psychoendocrinology. This was a con scious effort since some areas have received competent coverage in other volumes. In other instances, we have presented hitherto seldom mentioned material. For example, we are presenting coverage of the general areas dealing with hormones and behavior in aging and the aging process, mental illness, early experience, motivation, genetics and personality. In some instances, the available data is overabundant; in others, the data is scarce. However, we hope that an evaluation of this situation stimulates further interest and further collaborative research where needed.

This redesigned and expanded third edition of Diabetes Snacks, Treats, and Easy Eats for Kids offers even more simple, delicious recipes for healthy, well-balanced diets. Since the book was first published in 2006, the prevalence of diabetes in children has continued to increase. Children under age 19 have seen a 21 percent increase in Type 1 cases, and children ages 10-19 have seen a 30 percent increase in cases of Type 2-a disease that used to be considered an adult condition. But kids will be kids, and when they come home from school, they want a snack that's simple, satisfying, and occasionally sweet. When it comes to dinner, they usually don't have the time or the taste for fancy meals. With this in mind, author Barbara Grunes has developed more than 150 recipes for snacks and meals that kids really like and that stay within diabetic guidelines. Grunes's goal is to help all kids enjoy food that is good for them-even if they have diabetes. Each recipe includes the nutritional information readers need, whether they count carbs or use the exchange method. With recipes like Pizza Puffs, Spud Pancakes, Chicken Fajitas, Ice Cream Cone Cupcakes, and Fruit Turnovers, this book proves that everyone can enjoy familiar and delicious food together. After all, it's not about "good," "bad," or "forbidden" foods-it's about readers feeding their families sensibly.

We had the pleasure and the great opportunity to organize a symposium on "Molecular Biology of Brain and Endocrine Peptidergic Systems" under the auspices of the Canadian Biochemical society and the International Foundation for Biochemical Endocrinology. We were indeed very happy to ass ble a series of first rate speakers who delivered excellent papers on a variety of subjects from the synthesis of complicated peptide analogs, to the creation of trangenic mice, site-directed mutagenesis, enzyme characterization and DNA binding sites. One hundred and seventy-five participants attended the 40 conferences while having the opportunity to look at 24 posters presented by senior scientists as well as students. We, of the organizing committee, feel extremely pleased to have received an overwhelming response from such a group of scholars. We wish to express our sincere gratitude to Mrs. Diane Marcil who arranged most aspects of the meeting with efficiency. We also thank the different organizations and companies for their generous grants which made the reunion possible. We hope that the participants have gained scientifically while having a pleasant sojourn in beautiful Montreal. The organizing committee was made up of a group of dedicated people, particularly its secretary, Dr. Philippe Crine. To all speakers and sessions chairpersons, we are indebted for the excellence of their participation.

The beautiful town of Cavtat near Dubvronic, Yugoslavia was the site of the twelfth meeting of the International Foundation for Biochemical Endocrinology. It was sponsored by the Serbian Academy for Sciences and Arts and by the Foundation. The Croatia Hotel in Cavtat was a splendid place for a meeting. The presentation of the subject matter relating to "Neuroendocrine Correlates of Stress" was interesting and informa tive. The topics included many forms of stress, their mediators and responses. They included: releasing factors; neurotransmitters in the hypothalamus; role of noradrenal ine; the reaction of the hypothalamo-pituitary-adrenocortical axis to stress; immunological stress; thermal stress; immobil ization stress; peptides in shock; stress-induced prolactin; stress and acupuncture; stress and behavior; spinal cord transection and stress; electroconvulsive stress; neuroendocrine cells and stress; protein kinase as a signal transducer; the effects of constant 1 ight and darkness on the pineal; sleep, stress and ovarian function; and finally, hormonal response to exercise. Subsequently, the papers presented were rewritten for inclusion in this monograph. The Chairmen for the sessions at Cavtat were K. McKerns and Stefan Manolov, V. Chong-Li and L. Rakic, S. Feldman and R. Mil in, M. Lee and V. Liposits. The next meeting of the Foundation will be held in Edinburgh near the end of September, 1985. The topic will be "Neuroendocrine Molecular Biology" with Professor George Fink as Honorary Chairman of the local organizing committee."

This has been a year of substantial change for The Year in Endocrinology. The first change, though perhaps only a semantic one, nevertheless represents a landmark. Although last year's volume was designated as the first of an annual series, that seemed to me at the time merely a hope-a realistic hope, perhaps, but a hope, nevertheless. With the publication of this year's volume, however, this can accurately be said to be an annual series, one that we trust will fulfill a need and will therefore continue for years to come. Among other changes from last year's volume are some that were originally intended and others that were unintended. In the former category is the substitution of a chapter on water metabolism and vaso pressin, excellently prepared by Dr. Gary L. Robertson, for the chapter on paraendocrine syndromes that appeared last year. Chapters on these two topics will continue to appear on alternate years. Obviously, the non recurring chapter on a topic of special interest has also changed, and this year's comprises a comprehensive review of autoimmune endocrine dis ease by Drs. Jay Silverberg and Robert Volpe. The unexpected change results from the inability of Dr. Louis Avioli to continue as a member of the Editorial Board. Most fortunately, however, we have persuaded Dr. Charles R. Kleeman to join the Board and to be responsible for the chapter on the parathyroid gland and mineral metabolism. Dr. Kleeman has been assisted on the preparation of this chapter by his daughter, Dr."