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.

Inhibin, activin, and follistatin were originally discovered as hormonal fac- tors a decade ago. Subsequent studies revealed that they are widely distrib- uted anatomically and have multiple biological functions in a wide range of cells and tissues. Since the last Symposium three years ago, there has been remarkable progress toward defining activin's roles in controlling hormone secretion, cell differentiation and proliferation, mesoderm induction in em- bryos, nerve cell survival, and promotion of bone growth. Furthermore, the characterization of activin receptors as serine and threonine kinases and the identification of intracellular mediators such as the Smads have provided key elements for the eventual understanding of signaling mechanisms for activin and the other members of the TGF-beta superfamily. The unknown in this integrative field, however, remains far greater than the known. For ex- ample, we are just beginning to exploit the recently improved activin, inhibin, and follistatin two-site assays for the evaluation of the physiological and pathophysiological functions of these proteins. Also, we have only a rudi- mentary understanding of the mechanisms by which inhibin blocks activin, and many steps in the pathways linking the formation of ligand-receptor(s) complexes to transcriptional regulation are unclear. The aim of the Third Symposium was to bring together scientists from diverse fields to share technical and conceptual developments. The program was framed with the intention to include a wide range of timely research topics.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

In September of 1977 scientists from many countries met at the Asticou Inn in Maine to present and discuss papers written especially for this monograph. The presentations were informal and directed to the special interests of the audience in order to generate discussions. The authors, many of whom are pioneers and leaders in their field, then had the oppor tunity to revise their contributions, which were brought together with the edited discussions to form this volume. The basic research studies presented here are important because of the essential role of gonadotropins in regulating the ovary and testis. This monograph will therefore be of interest to those concerned with fertility regulation, population control, possible new methods for contraception, and to those concerned with reproduction in domestic animals. Re searchers in other fields may find this monograph useful, as it has been de termined that gonadotropins are secreted by many tumors and are im plicated in many cancers. Human choriogonadotropin also seems to be found in most, if not all, cells of the human body. The significance of this, however, is unknown."

Calcium-Sensing Receptor provides an overview of various aspects of the calcium receptor's biochemistry, physiology and pathophysiology that is suitable both for those who have been working in the field of Ca2+0-sensing as well as those who are new to this discipline. Calcium-Sensing Receptor is the nineteenth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.

"Theoretically, one should obtain essentially the same clinical picture from failure of an end-organ to respond to a hormone as from a decreased production or absence of said hormone. " With these words, Fuller Albright began his now classic paper describing a novel disease, pseudo hypoparathyroidism (PHP), and a novel concept, hormone resis- tance as a cause of disease. Soon, other hormone resistance disorders such as nephrogenic diabetes insipidus (NDI) were recognized, and the concept was extended to resistance to other substances such as calcium ions in familial hypocalciuric hypercalcemia (FHH). Later, diseases characterized by excess rather than deficient hormone action such as McCune-Albright syndrome (MAS) and familial male precocious puberty (FMPP) were recognized to be caused by autonomous endocrine hyperfunction. Although many i!!vestigators provided careful and detailed descriptions of the clinical features of these and other related endocrine disorders, an understanding of pathogenesis proved elusive for many years. In just the past few years, we have gone from clinical description to a molecular understanding of these interesting disorders. This remarkable progress reflects a synthe- sis of three distinct, but now overlapping, areas of biomedical research: the aforemen- tioned recognition and careful clinical description of specific diseases, the elucidation of the basic mechanisms of signal transduction, and the application of the powerful tools of molecular biology and genetics. Fundamental studies on the mechanisms of hormone action by Rodbell and colleagues at NIH culminated in the discovery of a major signal transduction pathway involving heterotrimeric G proteins.

An enormous amount of research effort has been directed toward elucidating the mechanism by which substances are extruded from cells; and reviews have been written and symposia held in order to systematize the plethora of evidence made available. However, the approaches employed to study the secretory process have been so diverse that it is difficult, if not impossible, for one individual or even a group of individuals to keep abreast of all aspects of the field and to analyze them critically. Thus I undertook the writing of this volume with a great deal of trepidation. In searching for some starting point, I naturally considered as my primary focus the role of calcium in the secretory process, which has occupied my research interests for the past 13 years. But since so much experimentation has been carried out on this and related topics during the last decade or two, I felt it was still necessary to visualize this venture from two alternative ap proaches: (1) a more general one, which would cover the subject of calcium and the secretory process from a broad perspective, but of course not in great detail, and (2) a more specific one, restricting coverage to carefully defined limits but with comprehensive analysis of limited topics. The final course undertaken appears to lie somewhere between these two extremes."

Most of the following chapters were presented as plenary lectures or symposium talks at the 1986 XXXth Congress of the International Union of Physiological Sciences in Vancouver, B.C. A distinguished international group of endocrinologists and physiologists have contributed up-to-date reviews of their particular fields. The early chapters are largely concerned with the brain and neuroendocrine mechanisms controlling the secretion of gonadotropin releasing hormone (GnRH) and its action on the anterior pitui- tary gland. Later chapters focus on the gonads themselves and the systemic and intrinsic hormones influencing the functional cytology of ovarian and testicular cells. Such comprehensive subjects as sex differentiation, puberty, placentation and parturition are also discussed authoritatively. According to Pfaff and Cohen and Arai et al., gonadal steroids, especially estrogen, exert multiple effects on certain hypothalamic and preoptic neurons, including growth, protein synthesis and electrical changes, which promote plasticity and facilitate synaptogenesis. The electrophysio- logy of the hypothalamic GnRH pulse generator in the rhesus monkey is reviewed more specifically by Knobil. In ovariectomized ewes, Clarke finds both positive and negative effects of estrogen on hypothalamic release of GnRH as well as on pituitary responsiveness to the peptide. Flerk6 et al.

Brain Neurosecretory Cytokines: Immune Response and Neuronal Survival summarizes the biological and chemical data of signal molecules of the brain neuroendocrine immune system, mainly proline-rich peptides, which play an important role in the regulation of immune response, neuronal survival, hematopoiesis, and adaptation. The author also describes the role of PRPs for the protection of neurons against neurodegenerative disturbances and diseases. Brain Neurosecretory Cytokines: Immune Response and Neuronal Survival will be of great aid to the researchers and students in various areas of neurobiological profile (neurochemistry, neuroendocrinology, neurophysiology, and endocrinology).

This book discusses contemporary features of ject, creating, therefore, a lacuna the could be diagnosis of endocrine diseases using the filled by this project. radiologic technique of percutaneous venous This book is intended to be a practical guide blood sampling for hormone assay. A compre- for vascular and interventional radiologists, in- hensive survey of the field is provided by the ternists, surgeons, endocrinologists, and other contributing authors, who have considerable physicians who care for patients with endocrine expertise in the subject. Some have published diseases. The intention is to provide a practical several articles in the literature; others have text covering anatomical data, clinical prob- extensive clinical experience. lems related to the diagnosis of the endocrine The approach to many of the endocrine dis- diseases, patient preparation for the sampling, eases has been markedly improved ~uring the blood sampling techniques, sample manipula- last two decades because of selective venous tion and storage, laboratory data, and clinical blood sampling, not only in the diagnosis of the significance of the hormone sampling and condition but especially in the precise localiza- assay. tion of the hormone-producing lesion and its clinical significance. Scattered informationbn venous blood sam- pling is available in the literature, but there is Renan Uftacker no comprehensive text dealing with the sub- Reingard Sorensen Contents Preface v Contributors xi 1 Selective Venous Sampling for the Differential Diagnosis of Female Hyperandrogenemia 1 Lathar Moltz and Reingard Sorensen Introduction ...1 Diagnostic Procedures ...2 Indications ...4 Anatomy and Anatomical Variations...

This book represents the proceedings from a conference that took place in Dallas in the spring of 1999 which was entitled "Pediatric Gender Assignment - A Critical Reappraisal". Some participants rightfully argued that the conference really focused on the issue of pediatric gender assignment, and that reassignment was not applied in most cases. Their comments were reflected in the title of this monograph. This multidisciplinary meeting was sponsored by a conference grant from the National Institutes of Health, and a broad inquiry into this complex topic took place from many points of view. Basic scientists offered insight into mechanisms of sexual differentiation of the gonads, physical phenotype and imprinting of the central nervous system. Endocrinologists reviewed their experience in diagnosis and management, surgeons described traditional as well as innovative approaches, and there was strong representation from the ethical and behavioral sciences. In putting together such a panel, it was essential that we identify a cast of speakers who could address their viewpoints with strong convictions, and yet not let their passions render the meeting counter productive. We were not disappointed. While many differing points of view were firmly expressed by the panelists and audience, all viewpoints were accorded the respect they deserved. The concept behind the meeting and this book really originated in 1997 shortly after Diamond and Sigmundson published their long term follow up study of the John/Joan case.

This book provides a concise summary across all aspects of endocrine surgery, covering the major endocrine organs and discussing aspects of surgical care. It comprises five sections covering the major endocrine organs/systems, each with a specialist section editor. Within each section there are a number of brief (2-3 page) chapters, written in a combination of prose and bullet points, a format that is conducive to both detailed reading and quicker, "dipping in", review. Each chapter contains a "Pearls and Pitfalls" summary box. The text takes into account the latest evidence and current expert opinion from an internationally renowned list of authors.

Stephen P. Ethier and a panel of leading investigators comprehensively analyze the cellular, molecular, and endocrine factors in the development of cancers of the breast, prostate, endometrium, and ovary. Concentrating on defining the most important unresolved issues in the field, the authors review how steroid hormones function to regulate normal mammary gland homeostasis in humans, with particular emphasis on the roles of estrogen, progesterone, and growth factors. Comprehensive and up-to-date, Endocrine Oncology offers both basic and clinical researchers not only the latest molecular and cellular findings on endocrine cancers, but also a powerful critical analysis that will prove invaluable to all endocrinologists and oncologists working in the area today.

In a state-of-the-art synthesis of basic science and clinical practice, Roy Smith and a distinguished panel of researchers and clinicians review GH regulation and its action at the molecular level, and describe the basis for GH deficiency and the use of GH as therapy in a variety of clinical situations. The clinical presentation moves beyond the treatment of GH-deficient children to include the genetics of GH-deficiency, GH-deficiency in adults, osteoporosis, Syndrome X, sleep quality, GH in AIDS patients, GHRH in clinical studies. Timely and innovative, Human Growth Hormone: Research and Clinical Practice will benefit both basic and clinical researchers, as well as those clinical endocrinologists who want to use growth hormone not only in treating children, but also in treating adult disorders, including those associated with metabolic disease.

The present volume is the results of 6 years' work by our team, during which time 2300 CT scans of the pituitary region were carried out. This was made possible by the close collaboration between physicians and technicians in our neuroradiological department, as well as by numerous corresponding physi cians. We wish to express our gratitude for their confidence and our sincere thanks to our colleagues at Besan90n, Dijon, Grenoble, Lyon, Montpellier, and Strasbourg. Furthermore, we especially wish to thank the patients who willingly accepted the difficult requirements of these studies. We are grateful to the technicians at the Neuroradiology Department of the Centre Hospitalier et U niversitaire de Besan90n, who have perfected the methodology so as to meet the ever increasing imperatives for precise anatomical mapping of the pituitary gland and the surrounding region; without their efforts, this book would never have been possible. Finally, we wish to express our thanks to the medical photographer of our group, as well as the secretarial staff for their contribution to the successful production of this work. We thank Labora toires Guerbet and General Electric for their excellent assistance, and Springer Verlag for their care and competence in the production of this book. In writing Computed Tomography of the Pituitary Gland, we have sought to develop morphological study of the pituitary gland to a degree of reliability comparable to that of laboratory findings in endocrine disorders.

During the last ten years, the diagnostic approach to disorders of bone and mineral metabolism has benefited considerably from the development of radioimmunoassay and competitive protein- binding techniques for measurements of circulating parathyroid hormone, calcitonin, and biologically active vitamin D me- tabolites. Accumulated experiences with radiogrametrical and densinometric methods of quantitating appendicular bone mass now facilitate the detection of changes in bone mineral content heretofore unrecognized by routine roentgenographic vertebral analysis. During this same decade, the diagnosis of metabolic bone disease and the skeletal response to remedial therapeutic ma- neuvers have also been facilitated by the routine application of the bone biopsy. Improvements in tinctorial techniques, stan- dardization in methodology essential for adequate preparation of thin undecalcified specimens, and the incorporation of tetracy- cline bone formation or mineralization "markers" should now herald the "routine" use of this diagnostic procedure. Moreover, the compilation and ready availability of reference morphometric data, spanning the prepubescent years charac- terized by skeletal growth and remodeling and the later senes- cent period during which bone loss normally proceeds in an un- 7 8 FOREWORD relenting fashion, allow adequate differentiation between normal age-sex-related changes in skeletal turnover attendant on skeletal maturation and aging and acquired or inherited de- rangements in bone metabolism.

Autoimmunity is the most common cause of endocrine disorders. This volume provides an up-to-date summary of recent advances in this important field. In addition, it describes developments in our understanding of conditions such as vitiligo and pernicious anaemia which are frequently associated with autoimmune endocrinopathies. There is a detailed review of animal models of endocrine disease which have contributed greatly to current knowledge. Furthermore, the aetiology, pathogenesis and treatment of the clinical disorders are discussed in depth. The book will be of interest to anyone working in the areas of endocrinology and immunology.

This book includes the most significant contributions of the First International Symposium on "Multiple risk factors in cardiovascular disease", chaired by Professors A. V. Chobanian (Boston), A. M. Gotto Jr. (Houston), c. Lenfant (Bethesda), R. Paoletti and A. Zanchetti (Milan), held in Washington DC, 10-12 December 1990, which focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological evidence that individuals from industrialized countries often possess two or more risk factors which synergically increase the global risk profile. The evidence that isolated vascular risk factors are not commonly found in high risk patients but more often a combination of risk factors are detected, is highlighted. Many recent epidemiological data identifying the intrinsic and environ mental factors contributing to the development of atherosclerosis are discussed. These results, in parallel to basic and clinical research, underline how atherosclerosis is a complex and multifac torial process involving the influences of lipid deposition, blood pressure, rheologic forces, carbohydrate tolerance, and thrombogenic factors (fibrinogen and platelets). Atherosclerosis is markedly accelerated by other risk factors, more so in the presence of concomitant hypercholes terolemia, hypertension, diabetes, upper body obesity. Furthermore, the risk associated with anyone of these risk factors varies widely depending on level of the associated atherogenic risk factors.

"Neuropeptides and Stress" presents a comprehensive survey by leading pioneers in the field of the knowledge and concepts implicating neuropeptides in the regulations of responses to stress. Topics covered include: recent advances on the regulation and modulation of the behavioral, endocrine, autonomic, gastrointestinal, immune and analgesic responses to stress by neuropeptides. Neuroanatomical and biological data are considered. Special emphasis is given to corticotropin-releasing factor (CRF) and opioid peptides.

From an award-winning endocrinology pioneer and metabolism expert comes a revolutionary, sustainable and scientific approach to help you lose weight, regain energy, clear your mind, and prevent disease.

Like our fingerprints, each of us has a unique metabolism. Your metabolism will change as you move through life, shaping your mental and physical capabilities. However, one in four of us will experience trouble with our metabolism. Dr. Noel Maclaren, an award-winning endocrinologist and Sunita Singh Maclaren, a medical anthropology expert, share their revolutionary new approach to mastering your metabolism that combines medical and behavioral insights in order to help balance your weight, boost your energy and improve your cognitive abilities.

Imagine the metabolism as a beguiling jigsaw. We all fit into one of four ‘metabolic personality’ types, based on our bodies' levels of sensitivity to insulin. Maximize Your Metabolism offers a comprehensive self-assessment quiz to uncover yours. Drawing on pioneering data from a person’s genetic legacies, appetite signals and mental resilience, this book will enable you to create a unique plan specific to your needs, and will help you achieve robust brain and body health, including:

• Enhancing your cognitive abilities by limiting grains and fruits as the brain’s ability to absorb glucose declines from your late 40’s onwards
• Optimizing your weight by identifying the simple vs. complex carbohydrates that work for your metabolic type
• Overcoming insulin-related persistent fatigue and increasing your muscle’s energy efficiency through resistance and aerobic exercise
• Protecting yourself from disease-causing internal inflammation by opting for prebiotics found in artichokes, leeks and onions and avoiding certain “health” foods

Dr. Noel Maclaren and Sunita Singh Maclaren have helped thousands of patients in their clinic for over fifteen years, by reversing these metabolic imbalances. Filled with specific time-tested guidance and over 30 healthy and delicious recipes, Maximize Your Metabolism is perfect for anyone who wants to be a champion of their own health, gain an overall sense of wellbeing in as little as six months, and to sustain it for a lifetime.

In Cushing's Disease, leading authorities in the field offer a thorough review of the pathogenesis, diagnostic algorithm and treatment options for this complex disease. Beginning with a fascinating history of Cushing's disease that outlines its historical significance to both endocrinology and neurosurgery, the book goes onto to cover the full range of important issues, including the molecular pathogenesis of Cushing's, anatomic pathology, the diagnosis of Cushing's syndrome, the differential of pseudo-Cushing's syndromes, hypercortisolemia, surgical removal of the corticotroph adenoma, post-operative management and assessment of remission, radiotherapeutic options, and the exciting developments in medical therapy. In addition, the book also addresses Cushing's disease in the pediatric population, given that its clinical manifestations and impact on growth can be severe; silent corticotroph adenomas as a distinct clinical entity; diagnosis and management of Cushing's disease during pregnancy, bilateral adrenalectomy, and, finally, the long-term psychological manifestations of hypercortisolemia. Comprehensive and an invaluable addition the literature, Cushing's Disease is an essential reference for enhancing diagnosis and treatment of this debilitating disorder.

The past two decades have seen steady progress in our understanding of the pathogenesis of atherosclerosis. The role of low density lipoprotein (LOL) increase and of LOL receptor deficiency or malfunctions in familial hypercholesterolemia has been largely enlightened by the works of Brown and Goldstein. These authors postulated also that modification of LOL to a form recognized by the scavenger or acetyl-LOL receptor may be required for lipid loading of macrophage-derived foam cells in the lesions. A growing body of evidence suggests that oxidative modification of LOL could enhance its atherogenicity by its implication as a factor in the generation of foam cells. Thus, if the role of LOL in the pathogenesis of hypercholesterolemia was well established a great deal of information appears currently on new approaches such as the mechanisms leading to the accumulation of foam cells, the impact of LOL structural alterations, notably oxidation and the role of gene mutations of apolipoprotein Band/or LOL receptor The opening topic is devoted to these new avenues outlined in the field of hypercholesterolemia. The first part concerns the genetic aspects of atherosclerosis: mainly the genetics of apo 1 ipoprote ins , their transcriptional regulation, the amino acid mutations of the apo B gene and of the LOL receptor gene, the structural domains and the acylation sites of apoprotein B.

This book tells the story of diabetes, from ancient times to today, and provides an accessible introduction to the cause, treatment, and impact of the disease.Diseases have a history, and understanding that history helps us understand how best to treat and control disease today. Today's students are confronted with a panoply of often-frightening illnesses and afflictions - the Biographies of Disease series provides necessary information to understand the origin of various maladies, how they impact contemporary society, and how doctors and researchers from around the world are fighting to devise treatments to alleviate or cure these diseases.This volume, Diabetes, covers a disease that has been a common affliction from the beginning of recorded history, but has been increasing in its impact because of changes in diet and exercise, especially among the young. Diabetes examines all aspects of this disease, including: the diagnosis and treatment of diabetes from the ancient period to the present day; the definition of the various types of diabetes, and the role of glucose and insulin; diagnosis and treatment, with an emphasis on prevention for those at risk; the cultural impact of the disease - on individuals, on families, and on the economy; and, the state of current research on new forms of insulin, blood glucose meters, transplants, and weight control.The volume includes a glossary of important terms and a bibliography of accessible works that discuss the disease.

This volume of Molecular Biology of Hematopoiesis is dedicated to many inter national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. The continuous support of the Presidents of the meeting, Professor F. Takaku, President of Jichi University, and E. D. Thomas, Nobel Laureate, was greatly acknowledged, especially Professor Takaku, for his vision and support for development of gene therapy in Japan. New information on BMT for autoimmune disease and organ transplantation was presented at the symposium and is published in this volume. Several new findings on gene therapy/transfer into HSC were presented by E. F. Vanin and A. Nienhuis, K. Humphries, 1. A. Nolta, H. E. Heslop, and M. K. Brenner. Professors S. Asano and K. Tani presented new studies on gene transfer into primates. Among the highlights were the new papers on gene transfer presented by G. Wage maker, N. G. Abraham, and M. Onoderea from R. M. BJaese's group. The use of BMT for organ transplant and autoim mune disease was updated and a representative paper is presented in this volume."

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.