The Third Advanced Seminar in Neurosurgical Research was held in the Palazzo Pisani Moretta, Venice, Italy from 30th April to 1st May, 1987 and was devoted to "Neuroendocrinological Aspects of Neurosurgery." The general aim of these advanced seminars is to bring together European Neurosurgeons interested or involved in research work, either clinically, experimentally or both, in a given field in order to achieve in-depth informal discussions not possible in the more conventional large congress. In particular, these advanced seminars seek to provide high level teaching by experienced basic scientists, to provide "state of the art" assessment of the subject and to highlight areas of controversy that may be suitable for future research. A special effort is made to identify younger neurosurgeons through the auspices of the European Directory of Neurosurgical Research, who have a particular interest in the subject under discussion, not all of whom will have immediate access to the most advanced, modern technology. The topic of Neuroendocrinology was chosen because clinically it is an area of controversy that should be amenable to application of new techniques, including molecular biology. There is a tendency on the part of Endocrinologists not to appreciate always that disturbances seen by Neurosurgeons may be different and need special attention. Inevitably there has been a little delay in publication of the manuscripts but these have been updated appropriately.

Every year there are new and exciting developments in assisted human reproduction, but how much do we really know about the underlying causes of infertility? This volume explores recent progress in the understanding of the genetics of spermatogenesis and male infertility. Topics include fundamental advances and current problems in the development and function of the testis, an outline of clinical findings in male infertility and an overview of the role of the Y chromosome in male fertility. Comprehensive critiques of posttranscriptional control during spermatogenesis, mammalian meiotic sterility, and comparative genetics of human spermatogenesis from the perspective of yeast, Drosophila and mice provide a global overview of the field.

This book brings together some of the results and ideas produced by a large number of people-colleagues and students with whom I am privileged to work in the laboratory at Rockefeller University. In terms of my personal history I see it as a confluence of creative forces persons from whom I have learned. I was instructed in neuroanatomy by Walle J. H. Nauta at M. I. T., and later in a course at Harvard Medical School under the direction of Richard Sidman. At Harvard Medical School, where M. I. T. graduate students were allowed to cross register, the superb neurophysiology course was under the guiding spirit of Stephen Kuffler. Later, I benefited greatly from participating in his summer course in electrophysiological techniques at Woods Hole. Eric Kandel and his colleagues have provided us with the most exciting contemporary approach to the conceptualization and study of cellular mechanisms for behavior. Here at Rockefeller, Carl Pfaffmann and Neal Miller have been leaders in every sense of the word. Not only did they provide me with opportunities to grow to scientific maturity; they also set an example of clear thinking about mechanisms for mammalian behavior patterns. I wrote this book to show how the systematic use of increasingly detailed electrophysiological, neuroanatomical, and neuroendocrine tech niques can explain the mechanism for a mammalian behavioral response. The behavior in question happens to be sensitive to steroid hormones and plays a central role in reproduction."

Thyroid carcinoma is an uncommon malignan ing the available non-human lines, as models cy. In the vast majority of patients, if treated for cell cycle studies and oncogene/anti appropriately, it is associated with a benign oncogene regulation, because they are unaware clinical course. Why then does it hold a con of the often fundamental dichotomy between tinuing fascination for so many physicians? thyroid malignancy and prognosis. Third, the The answer is probably directly dependent very nature of the benign clinical course has suggested to the major health research fund on the very benign nature of most thyroid ing agencies that thyroid cancer is not worthy maligllancies. While there are terrible excep of study in a time of scarce resources. tions, the follicular and papillary thyroid can Nothing could be further from the truth. cers behave in a way quite alien to "common" This gratifying clinical course is the very reason neoplasia, since they grow and metastasize why the study of human thyroid cancer has the slowly. We believe that if only we could under potential for contributing further to our fun stand such a transformed state, we would be able to learn a great deal about the normal and damental understanding of malignancy and, abnormal regulation of the cell cycle and im perhaps more importantly, the mechanisms by prove our understanding of cancer. which the human body can resist neoplastic However, recent advances in the biology of cells."

Neuroendocrine Perspectives, Volume 7, is part of an international book series designed to keep clinicians and researchers appraised of important trends and new data in basic and clinical neuroendocrinology. It focuses on four very rapidly evolving major topics: - the role of dopaminergic regulation of the intermediate pituitary lobe in elucidating intracellular signal transaction pathways and other regulatory mechanisms involved in transsynaptic regulation of peptide biosynthesis, post-translational processing, and hormone secretion; - the physiological and clinical implications of corticotropin releasing factor for such areas as diagnosing Cushing's syndrome, defining the hypothalamic and pituitary origins of secondary adrenal insufficiency, and distinguishing Cushing's syndrome from psychiatric states associated with hypercortisolism; - the large number of neurotrophic factors that affect CNS neurons and of neurite promoting factors that modulate neuronal performance, with emphasis on their mechanisms of action and their possible therapeutic applications to peripheral neuropathies and central diseases; - and the many factors that regulate changes in female reproductive cycles during middle age, with careful distinction between neuroendocrine and ovarian components and special attention to the possible cause-and-effect relationship within the cascade of events resulting in acyclicity and infertility.

One of the hallmarks of aging is the decreased capacity to adapt to changes in the environment. In a constant, controlled environment, it is often difficult to distin guish the functioning of the young organism from that of the old. However, when stresses are applied-temperature stresses, dietary stresses, infection, emotional stresses-the differences are more apparent. Frequently, the response ofthe old is delayed and may never reach the same mag'nitude as the young. These responses, in most cases, are mediated by the neuroendocrine system, which communicates via hormones, neurotransmitters, and related substances. Thus, it is important to understand the age-related changes that take place in the secretion and act ion of these substances and how these changes relate to the well-being of the whole organism. Indeed, the "neuroendocrine theory of aging" proposes that almost all of the characteristics of aging can be accounted for by dysfunction of the neuroendocrine system. A book on endocrine function and aging is particularly relevant at this time. With the advent of the techniques of molecular biology, there has bee an explo sion of knowledge concerning hormone secretion and action. Hormones, pro hormones, hormone receptors, and "second messenger" mediators rapidly are being cloned and sequenced. Such knowledge gives us important insights into the molecular workings of these substances as well as into the genetic hasis of endo crine dysfunction. These new tools are now being applied to the problem of age related changes in endocrine function."

The fact that certain adrenal steroid hormones are immunosuppressive and anti-inflammatory has been known for many years, and is routinely exploited by physicians. These effects are attributable to glucocorticoid steroids such as cortisol. Pharmacological doses of glucocorticoids inhibit most or all T cell types. However we now know that the effect of exposure to raised physiological levels is mainly to drive developing lymphocyte responses towards a Th2 cytokine profile (interleukin-4 secreting) while suppressing the development ofThi (gamma interferon- secreting) lymphocytes. Only recently have two further regulatory mechanisms become appar- ent. First, these effects of cortisol are balanced by pro-inflammatory and ThI-enhancing effects of another adrenal steroid, dehydroepiandro- sterone sulfate (DHEAS). Second, the activity of cortisol is directly modulated by enzymes in the target organs and lymphoid tissues that convert it into inactive cortisone. This new information leads to the possibility that immunoregulatory steroids could be used by physicians in novel ways. We can envisage steroid combinations that exploit the anti-inflammatory effects of corti- sol, while the Thi-suppressing and Th2-promoting properties of these hormones are opposed by derivatives of DHEAS. Such therapies are already proving effective in animal models of infection, and could revol- utionize treatment of Th2-mediated diseases such as asthma, where the anti-inflammatory effects of cortisol are desirable but the effects on T lymphocyte differentiation are not.

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.

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.

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.

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.

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."

A critical review by prominent experts of both the cutting-edge of stem cell biology and the application of stem cells to endocrine diseases, including diabetes, infertility, and liver-associated metabolic disorders. The authors discuss current research to modify stem cells, develop an endocrine-like cell, and use adult bone marrow stem cells to treat autoimmune diseases, including endocrine-based autoimmune diseases. Topics of interest include a review of all stem cell subtypes and their characteristics, approaches to promoting endocrine development from stem cells, and evidence for endocrine cell function from stem cells. The authors also outline how best to develop preclinical studies that will determine the safety and efficacy of stem cell therapies for endocrine disorders.

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.

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.

Until recently, endocrinology and critical care medicine were two specialties in medicine that were rather uncomfortable with each other and hence quite i- lated. Fortunately, these two 'alien' disciplines have joined forces in successful attempts to perform high quality research in order to clarify the unknown. By integrating endocrinology in critical care medicine, or vice-versa depending on the specialty of the observer, new experimental and clinical data on the complex endocrine and metabolic derangements accompanying non-endocrine severe i- nesses came available which generated important novel insights with relevant clinical implications. In addition, the state of the art diagnosis and management of primary endocrine diseases that represent life-threatening situations leading to ICU admission has been updated. This issue of Contemporary Endocrinology aims at compiling the new ?ndings. The book indeed covers both areas of 'Acute Endocrinology' that are often taking care of at very distant sites within hospitals. The ?rst part deals with the classical life-threatening illnesses caused by primary endocrine diseases such as thyrotoxicosis, hypothyroidism, acute adrenal crisis, acute calcium disorders, pheochromocytoma, severe hyper- and hypoglycemia . The second part looks at endocrinology from the ICU side, starting with a g- eral overview of the dynamic neuroendocrine and metabolic stress responses in the condition of intensive care-dependent, non-endocrine critical illness.

There is currently no single book with up to date information on osteoclast function and bone resorption.

A useful collection of information, not readily available in a concentrated and convenient form on the market.

Provides a comprehensive overview of the field.

Roger Cone and a distinguished team of expert investigators provide the first major treatment of this critically important receptor family. The book illuminates the structure and function of these receptors through a wide-ranging review of the latest findings concerning the biology, physiology, and pharmacology of their peptide ligands and covers the major melanocortin peptides, Melanocortin-1-Receptors through Melanocortin-5-Receptors. Topics include the characterization of the melanocortin receptors, the biochemical mechanism of receptor action, and receptor function and regulation. Timely and authoritative, The Melanocortin Receptors offers an up-to-date knowledge base on the remarkably complex structure and functions of the melanocortins, a guide that will prove invaluable for today's neuroscientists, endocrinologists, pharmacologists, and other clinical and experimental investigators working in this fast moving field.

Both thyroid dysfunction and heart failure show a high prevalence in the adult population. Frequently, in clinical practice, a multidisciplinary approach is useful to optimize the management of patients with these conditions. Although there is no doubt regarding the close link between cardiovascular pathophysiology and thyroid homeostasis, our understanding of this association is far from being exhaustive. Thyroid hormone regulates the expression of cardiac-specific functional contractile and structural proteins and plays a pivotal role in modulating both diastolic and systolic function as well as peripheral vascular resistance. The close relationship between thyroid and heart dysfunction is strongly supported by recent evidence demonstrating that an altered thyroid profile is a negative prognostic predictor in patients with heart failure. The treatment of chronic heart failure, especially in advanced stages of the disease, continues to be an open and challenging field. The potential of novel thyroid hormone therapies that address the molecular biology of thyroid dysfunction and heart failure thus represents an attractive area of multidisciplinary scientific interest. This book is a readable, integrated, and highly up to date presentation of the clinical, pathophysiological, and basic science aspects of thyroid-heart failure interactions. It addresses a complex subject in an approach that targets a large audience of readers.

Over the last decade it has been shown that orphan G protein-coupled receptors (GPCRs) can be used as targets to discover novel neuropeptides. A dozen neuropeptides have been identified through this approach. Each of these neuropeptides has opened new doors for our understanding of fundamental physiological or behavioral responses. For example the orexins, MCH and ghrelin carry fundamental roles in regulating food intake while neuropeptide S, neuromedin S, the prokineticins and the orexins are major players in modulating sleep and circadian rhythms. The chapters of this book review the latest research in the field, most of them are written by the original discoverers of the respective novel neuropeptide. Emphasis is set not only on their discovery but also on their functional significance. Since many of these neuropeptides are part of drug discovery programs, this book impacts academic as well as pharmaceutical research.

Skin lesions are often the first sign for an endocrine disease. Their description is thus of relevance for early diagnosis and treatment of endocrine disease for specialists in endocrinology as well as in dermatology.

Lavishly illustrated, this book describes the clinical and histological features of skin lesions observed in endocrine diseases. All features are reader-friendly structured and written in the language of dermatologists in order to enable a simple association between the features observed and the endocrine etiology.

Modern cardiovascular science has produced a revolutionary new idea: the heart acts not merely as a pump, but as a "gland," that is as a regulator of circulatory homeostasis and salt-water balance. This book combines the classical heamodynamic view with the new neuro-hormonal paradigm, in all its potential clinical implications. The book will interest physiologists and clinicians involved in the study of the cardiovascular system and care of heart patients.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together provide important insights to our understanding of hormonal cancer causation, development, and prevention; the primary objective of these Symposia. A special emphasis is placed on the two major endocrine-related cancers, that is, breast and prostate. The emerging fields of colon, lung, and pancreatic cancers in relation to hormones are examined.