Congenital adrenal hyperplasia (CAH) consists of a group of disorders of adrenal steroidogenesis. Each disorder results from an inherited deficiency of one of the several enzymes necessary for normal steroid synthesis. The different enzyme deficiencies produce characteristic patterns of hormonal abnormalities; the clinical symptoms of the different forms of CAH depend on the particular hormones that are deficient or that are produced in excess. The earliest documented description of CAH was by DeCrecchio in 1865 (DeCrecchio 1865). This Neapolitan anatomist described a cadaver having a penis with first degree hypospadias but no externally palpable gonads. Dis- section revealed a vagina, uterus, fallopian tubes, ovaries, and markedly enlarged adrenals. It is interesting that the subject suffered a confusion of sex assignment, being declared a female at birth and a male 4 years later. He conducted himself as a male sexually and socially. Since the original descrip- tion of this case, investigators have unravelled the pathophysiology of the inborn errors of steroidogenesis. 1 Steroidogenesis and Enzymatic Conversions of Adrenal Steroid Hormones A. Steroidogenesis The adrenal synthesizes three main classes of hormones: mineralocorticoids (17-deoxy pathway), glucocorticoids (17-hydroxy pathway), and sex steroids.

The present monograph will concern itself with those disorders of the endocrine system, either associated with destruction, interference with function or hyper- function, which are considered to be due to auto-immune processes. Endocrinopathies Non-endocrine auto-immune disorders associated with the endocrinopathies Graves' (Basedow's, Parry's) disease Pernicious anaemia Hashimoto's thyroiditis Vitiligo Idiopathic Addison's disease Myaesthenia gravis Insulinopenic diabetes mellitus Sjogren's syndrome Auto-immune oophoritis and orchitis Rheumatoid arthritis Auto-immune hypoparathyroidism Idiopathic thrombocytopenic purpura Auto-immune hypophysitis Chronic active hepatitis Possibly some cases of infertility Primary biliary cirrhosis due to anti-sperm antibodies Reproduced with permission from Volpe (1977) The above table indicates those organ-specific endocrinopathies considered to be due to auto-immune factors, as well as those non-endocrine, organ-specific auto-immune disorders which may be associated with them (Volpe 1977). It is evident that such disorders, occurring without any obvious external cause, raise the very elementary question of how immune processes directed against self- constituents could be initiated. Generally, of course, the immune system acts as a regulatory and defence mechanism, and disorders of auto-immunity represent breakdowns in this regulatory system. The following chapters will be concerned with the individual components ofthe endocrine system so affected by auto-immune processes; it will first be necessary to provide an initial chapter for the purpose of summarizing some general principles of immunology, in order to place the immune disorders of the endocrine system in context.

The findings of immunogenetic linkages, autoantibodies including autoislet cell and autoinsulin antibodies-and viruses in diabetes has attracted increasing interest among immunologists, virologists, geneticists and clinicians. To gather together the recent avalanche ef new and exciting information emerging in this area, Current Topics in Microbiology and Immunology has put together two volumes on this subject. The first volume, CTMI 156, (see page VI for contents) provided data on the animal models and experimental approaches currently employed to evaluate both the autoimmune and virologic factors contributing to the causation and patho genesis of diabetes. The second is this current volume. It is edited by Drs. BAEKKESKOV and HANSEN and focuses on current knowledge in human diabetes. This volume on human diabetes contains ten chapters from leading researchers. The book is arranged in two components. The first part critically analyzes the genes in man that playa role in susceptibility to insulin dependent diabetes mellitus (IDDM). The second segment analyzes the role(s) that various environ mental factors play in IDDM and provides data on the autoantigens, aberrant immune responses, and the role of cytokines and free radicals in the pathogenesis of diabetes. La Jolla, California MICHAEL B. A. OLDSTONE, M.D. This collection of studies was conceived as part of a two-volume review of the immunology of diabetes. The contents of Volume 156, which forms part 1, are listed below."

It is a truism that as we age there are a number of underlying physiological changes conspiring to alter our level of behavioral and cognitive function ing. Despite the inherent interrelatedness of these behavioral and cognitive changes, all too often the papers we read confine themselves to specific, isolated components of the developing process. Although exceptions nat urally exist, we believe that these exceptions should become rule. Although an integrated approach is important in all areas of adult devel opment, it is perhaps particularly germane in the study of atypical aging. Here, changes in overall functioning can occur in rapid succession, with the synchrony of decline between different subprocesses making it difficult to factor changes in one process from changes in another. For example, because changes in cognitive functioning co-occur with other dramatic changes in (motoric) response capacities, it is unclear how one can effec tively study changes in the ability to cognize independent of changes in the very mechanisms (ability to execute motor sequences) so often used to index cognitive performance."

The tridecapeptide neurotensin (NT) was first identified in bovine hypothalamic extracts and characterized by Carraway and Leeman (1973,1975,1976) and has subsequently been found in all classes of vertebrates (Carraway and Leeman 1976; Kitabgi et al. 1976; Kataoka et al. 1979; Langer et al. 1979; Reinecke et al. 1980a; Cooper et al. 1981; Grant et al. 1982; Carraway et al. 1982; Eldred and Karten 1983), many invertebrates (Reinecke et al. 1980 b; Grimmelikhuijzen et al. 1981; Price et al. 1982), and certain bacteria (Bhatnagar and Carraway 1981). It is distributed throughout the mammalian central nervous system (CNS) (Uhl and Snyder 1977 a, b), gastrointestinal tract (Sundler et al. 1977; Schultzberg et al. 1980), cerebrospinal fluid (CSF), adrenals, pancreas, and plasma (Fernstrom et al. 1980). When administered systemically, the peptide has a variety of effects such as hypotension, hyperglycemia, decreased gastric acid secretion, decreased gut motility, and altered secretion of anterior pituitary hormones (Leeman and Carraway 1982). NT apparently does not cross the blood-brain barrier in appre- ciable quantities; however, when administered directly into the CNS, it produces a number of physiological and behavioral effects. A burgeoning body of evidence supports the role of NT as a neurotransmitter or neuromodulator. Thus far, het- erogeneous CNS distribution, release of NT upon neuronal depolarization, satu- rable and specific binding of NT to receptors, and degradation by peptidases have all been demonstrated.

Endocrinology and Metabolism: Progress in Research and Clinical Prac tice is a new series that has been designed to present timely, critical reviews of constantly evolving fields; to provide practical and up-to-date guidance in the solution of pertinent clinical problems; to offer an alterna tive to the laborious search of the literature (and the often frustrating reading of highly technical articles); and to translate the language of the laboratory into that of the practice of medicine. We think that this volume and those to come will prove useful to physi cians (and to physicians in training), as well as to investigators in a wide variety of specialties; in short, to anyone who seeks answers to questions in endocrinology and metabolism. The first chapter of this volume could well serve as a general introduc tion to the entire series. It points out how our growing understanding of the molecular basis of biologic communication has led to the discovery of a growing number of clinical syndromes, as well as to the realization that phenotypically similar diseases may have radically different pathogenetic mechanisms and thus may require radically different therapeutic strata gems."

Progress in basic research has made it necessary to redetermine the possibility of classic endocrine therapy for the treatment of patients with breast cancer. Exemplary, close cooperation between biochemis try and animal and clinical research led to a truly interdisciplinary and international exchange of ideas and experience at a symposium held in autumn 1978 in Heidelberg. We owe our thanks to ICI-Pharma for the kind support of this sym posIUm. The participation of Charles Huggins in the meeting as honorary chairman signified to all participants the meaning of this joint endeavour. It was the same Charles Huggins who through experimental work laid the foundation stone for endocrine ther apy of prostate and breast cancer, and who applied his findings clinically. Thousands of patients owe to him relief from their suffering. He contributed greatly to the attempt to find and stabilize the endocrine therapy for breast cancer, for which we thank him sincerely. We hope that the following contributions will similarly serve the well-being of our patients."

It is fourteen years since insulin was last reviewed in The Handbook of Ex perimental Pharmacology, in volume 32. The present endeavor is more modest in scope. Volume 32 appeared in two separate parts, each having its own subeditors, and together the two parts covered nearly all areas of insulin pharmacology. Such comprehensiveness seemed impractical in a new volume. The amount of in formation related to insulin that is now available simply would not fit in a reasonable amount of space. Furthermore, for better or worse, scientists have be come so specialized that a volume providing such broad coverage seemed likely in its totality to be of interest or value to very few individuals. We therefore decided to limit the present volume to the following areas: insulin chemistry and structure, insulin biosynthesis and secretion, insulin receptor, and insulin action at the cellular level. We felt these areas formed a coherent unit. We also felt, perhaps as much because of our own interests and perspectives as any objective reality, that these were the areas in which recent progress has been most dramatic, and yet, paradoxically and tantalizingly, these were the areas in which most has yet to be learned. Even with this limited scope, there are some major gaps in coverage. Regrettably, two important areas, the beta cell ATP-sensitive potassium channel and the glucose transporter, were among these. Nevertheless, the authors who con tributed have done an excellent job, and we would like to thank them for their diligence.

Research in diabetes has accelerated in two areas, both of which are being reviewed in CTMI. The first is the use of a variety of animal models; the second is basic research in human investigation, islet cell antigens, and mapping of genes as sociated with susceptibility to disease. Dr. Thomas Dyrberg accepted editorial responsibility for this volume, which covers the first area. A second book, to be published later in the year, is edited by Drs. Brekkeskov and Hansen (CTMI 164, see page VI for contents). Although the contributors to both volumes represent the international scientific community, the editors are from the Hagedorn Research Laboratory in Denmark. Work at this institute and the Steno Memorial Hospital has been dedicated to research in diabetes for decades, and the insti tutions were appointed WHO Collaborating Centres for Re search and Training on the Pathogenesis of Diabetes Mellitus in 1983. It is worth noting that while addressing the hypothesis of the role of class II major histocompatibility glycoproteins in autoimmune diabetes (insulin-dependent diabetes, IDDM) a number of investigators established animal models in which class II molecules were expressed under the control of the rat insulin promoter. While generating interesting information on 100M, the finding of immunologic tolerance in such transgenic mice has attracted the attention of several basic immunologic laboratories for quite different reasons. Thus, we are reminded again of the Pasteur dictum that "chance favors the prepared mind. " Michael B. A. Oldstone, M. D."

Dr. Raymond Pederson, Dr. Jill Dryburgh and I commenced work on GIP in 1968, when, with the generous help of Professor Viktor Mutt and Professor Erik Jorpes of the Karolinska Inst, itute, Stockholm, we were able to establish that there existed an inhibitory material for acid secretion in cholecystokinin-pancreozymin prepara tions. Once the physiological evidence for the inhibitor was established it seemed appropriate to seek help in its isolation. Dr. J. Dryburgh and Dr. R. Pederson were left to bioassay fractions in Vancouver whilst I enjoyed the company of Professor Mutt at the Karolinska for one year, as a Medical Research Council of Canada Visiting Scientist. Purification of the inhibitory factor proceeded rapidly due, in no small measure, to Professor Mutt's untirmg efforts on my behalf. Later that year, Dr. Dryburgh joined us in Stockholm to begin the sequence work on GIP. This was completed late in 1970 in Vancouver. In Stockholm in June 1970, I met a fellow Canadian Dr. John Dupre (McGill University) at a cocktail party who kept commenting about the possibility of GIP being an insulinotropic hormone, the "incretin" of earlier days. At that time, gastrointestinal physiologist as I was, I did not recognize the importance of his comment. This became apparent two or three years later when Dr. Dupre demonstrated that GIP was insulinotropic in man. In 1972, Maryanne Kuzio and Dr."

This monograph represents the first comprehensive review of hormones in human amniotic fluid and includes data published up to and including 1980. Recently, more extensive use of amniocentesis for prenatal diagnosis and evaluation of fetal lung maturation has shown that amniotic fluid hormone measurements can aid in the diagnosis of fetal and placental abnormalities. The material is presented in two main sections dealing with steroid and protein hormones. The methods of identification and quantitation are delineated, and the findings are discussed in relation to the clinical conditions. In addition, particular attention has been directed towards up-to-date review of the sources, metabolism and transfer of human amniotic fluid hormones. The review is intended to serve the needs of clinicians, basic scientists and students, providing detailed information on human amniotic fluid hormones in order to improve patient care and indicate possibilities for further investigations. Ttibingen, January 1982 A.E. Schindler Contents Introduction A. 1 Origin of Human Amniotic Fluid . 2 B. C. Origin and Regulation of Steroids in Human Amniotic Fluid . 5 D. Methods of Isolation and Identification of Steroids in Human Amniotic Fluid 6 I. C , C , and C Steroids . 6 30 29 28 II. C Steroids 6 27 1. Cholesterol 6 2. Cholestanol . 6 3. ,::l7 -Cholestenol and ,::l8 -Cholestenol. 6 4. 7-Dehydrocholesterol and Desmosterol . 6 ,::l5_C Steroids. III. 7 21 1. Pregnenolone 7 2. 16cx-H ydroxypregnenolone. 7 3. 17cx-Hydroxypregnenolone.

A. CORBIN Investigations on LHRH and its analogs have just completed their first decade. We have witnessed a veritable explosion of chemical, physiologic and pharmacologic data on this hypothalamic peptide and the approximately 1500 agonist and antagonist analogs that have been synthesized. In order to track this expanding field, I was asked to organize an international symposium on basic and clinical aspects of LHRH analogs as part of the Reproductive Health Care: CDS Symposium held in Maui, Hawaii, in October 1982. This meeting brought together a number of the leading investigators in the field. Much new state-of-the-art information was presented which I and my colleagues felt deserved a wider audience. Drs Vickery, Nestor, and Hafez consented to undertake this task. Upon review of the literature, it was apparent that there was no recent text which fully covered the breadth of developments in the field. Accordingly, the editors decided to use the symposium as a nucleus on which to build a singular, comprehensive state-of-the-art analysis of this rapidly growing discipline, and the application of such knowledge to reproductive medicine. As exemplified by the various areas of expertise provided by the individual contributors, it becomes obvious that the scope of the subject matter, while relating solely to a well-defined chemical class (LHRH analogs) and a circumscribed physiologic and pharmacologic entity (reproduction), has expanded enormously.

A large number of chemical agents are known which affect blood and blood-forming organs. The purpose of this volume is to review the sig- nificant advances made over the past several years regarding such chemical agents. The purification, biological action, and therapeutic implications of several widely used hematopoietic growth factors such as interleukin 3 (IL-3 or multi-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), colony stimu- lating factor (CSF-I or M-CSF), thrombopoietin, and erythropoietin are included in this volume. These factors are important in regulating several hematopoietic cell lines such as neutrophils, monocytes, eosinophils, macrophages, megakaryocytes, platelets, and erythrocytes. People are exposed daily to numerous toxic chemical substances present in our environment which produce a suppression of erythropoiesis, myelo- poiesis, lymphocytopoiesis, and megakaryocytopoiesis. Attempts have been made in this volume to assess the therapeutic role of some of the hematopoietic factors such as erythropoietin in the anemia of end stage renal disease, as well as colony stimulating factors in other hematopoietic abnormalities. In addition, some of the chemical factors in our environment which suppress major hematopoietic lineages stimulated by erythropoietin, macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin I-alpha, interleukin I-beta, and interleukins 2, 3, 4, 5, 6, 7, and 9 are also included. An updating of the mechanism of action of each of these factors on the major hematopoietic lineages is covered.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of on cology."

Describes the ability of a series of endocrine-derived compounds, i.e. CHRH, LHRH, somatostatin, anti-androgens, and aromatase inhibitors to exert a direct anti-neoplastic activity or to potentiate the activity of traditional chemotherapeutic agents on neuroendocrine and solid tumors. In addition, a new class of potent GH-releasers, GSHs/Ghrelin, endowed with important endocrine and extra-endcocrine action, is presented. Therefore, in addition to traditional chemotherapy, characterized by high toxicity and non-selective action on tumoral cells, the reader can find a new approach with more selective, less cytotoxic endocrine derived compounds.

The authors of this book have a goal-to describe the management of infertility from the perspective of physiology and anatomy gone awry. To accomplish this goal, the chapters devoted to the causes of infertil ity begin with a description of the normal structure and function of the organ or system causing the infertility. We believe that under standing the normal will result in rational and effective diagnosis and treatment of infertility. Our intent is that this book be a useful re source for those who care for infertile couples. For an infertile couple, success is the delivery of a normal and healthy infant. Chapters that describe the causes and treatment of habitual abortion and the reproductive performance of previously infertile couples emphasize the hazards that exist between conception and birth. Our environment is one of these hazards, one that may also affect reproduction before conception. A chapter is devoted to a de scription of environmental agents that affect reproduction, the mech anisms of their effect, and methods to predict those present and future environmental agents which might also affect reproduction."

Contraceptives have always provided ground for controversy. This book describes and discusses latest findings concerning the advantages as well as hazard and risk factors of contraception. The clinical impact of oral contraceptives on metabolism is particularly highlighted. In addition, behavioral methods, intrauterine devices, implants and modern approaches in animal and clinical research in the field of immunization against pregnancy are considered. Last, but not least, the book summarizes the complex ethical, religious and political aspects of family planning and contraception.

The Organon Symposia have actually become a tradition, keeping up with exciting developments in reproductive medicine. The purpose of this symposium on "Fertiliza tion of the Human Egg in Vitro" was to bring together the stilllimited number of elinical specialists in the field and to stimulate another group of basic research people to exchange their experiences and knowledge, hopefully promoting elose cooperation between the two groups. It was a kind of scientific "first" that all research teams so far successful in achieving the birth of a healthy baby, fertilized in vitro came together at a workshop conference without a large audience of spectators and reporters, but with a small number of highly critical colleagues from the fields of basic reproductive physiology and comparative developmental biology. This atmosphere allowed for the elose exchange of results, hypotheses, diagnostic and therapeutic procedures, criticism, and respect, and created very productive discussions, all of which furthered the aim of the method: To help more childless couples to have their own babies by the ultima ratio procedure of in vitro fertilization and embryo replacement. The book that has emerged from this symposium will help to disseminate the great amount of information and experience gathered among the scientifically and clinically interested colleagues of many other hospitals and universities who could not be invited to the meeting. At the same time, it will prove that there is much more work to be done in the basic and clinical sciences of human embryology and reproductive biology."

The various congresses on growth hormone (GH) which have been held in Milan since 1967, the Milan Congresses, have witnessed over 25 years the tremendous expansion of a research field that was based initially upon the scarce knowledge of the biological properties of a protein. GH, whose chemical structure had just been identified and a radioimmunoassay developed for its measurement in blood, became in the following years a major area of biological research. The boundaries have since become blurred, as the research area has extended to the physiology and pathology of growth, puberty and reproduction, and the control of metabolism during the whole lifespan. Since the last GH Congress held in 1987, GH studies using the molecular biological approach have resulted in the puri fication, cloning and expression of the human GH (hGH) recep tor and binding protein, in new and exciting information on the insulin-like growth factors (IGF) and their paracrine and autocrine roles, and in the awareness that a panoply of binding proteins are present in the extracellular fluids and can, possibly, modulate IGF-receptor interactions and, thus, IGF actions. Finally, the availability of large amounts of biosynthetic hGH, besides allow ing more extensive clinical use in states of GH deficiency and extrasomatotrophic pathologies, has permitted disclosure of im portant metabolic effects of hGH during adulthood and, perhaps, aging and in many protein catabolic states."

It is about 15 years since the first presentation on uteroglobin was given to a group of developmental biologists, reproductive physiologists, and geneticists who had gathered in November 1966 at Konstanz (Germany). In the following decade so much knowledge was accumulated that a special symposium seemed appropriate. This was organized as a satellite symposium to the International Congress of Endocrinology at Hamburg and brought together 50 scientists at Aachen. These scientists, working in the field of pro teins and steroids, in early pregnancy, recognized the impact of what had been reported, and many of them later agreed to contribute to this booN. and thus to present their research d, ta available until December 1980. The present volume covers a relatively broad spectrum of data and observations which shed some light on preimplantational embryonic life and on the supports and obstacles provided by the maternal organism with respect to final accomplishment of normal im plantation and establishment of pregnancy. The book will serve both as a textbook and as a scientific dictionary for Ph.D. students, postdoctoral fellows and advanced scientists working in this area. The course of early pregnancy depends very much on a proper balance of steroid hor mones, and the induction of protein synthesis by steroid hormones is one of the well known fundamental processes in cellular differentiation and embryonic development."

From the discovery of Pdx1, the first "master gene" of pancreatic development, to the most recent findings on the role of microRNAs in beta cell homeostasis, the last fifteen years have seen an unprecedented advance in our understanding of the precise development and organization of the many different cell types that make up the pancreas. It is now widely acknowledged that the therapeutic differentiation of stem cells into pancreatic cells is an ambitious endeavor that will not succeed without a thorough understanding of the molecular processes underlying the native development of the organ. This book, aimed at experts and students alike, offers a comprehensive review of the state of the art in both pancreatic development and regeneration. The many strategies to differentiate adult and embryonic stem cells into pancreatic beta cells are also discussed in the context of potential therapeutic interventions for type I diabetes.

Sixteen years is a long time, not only in human life but also in the rapid history of contemporary endocrinology. Since the publication of the first edition of this monograph, numerous new lines of research and discoveries have greatly contrib- uted to our knowledge of the physiological and pathological regulation of aldos- terone biosynthesis in man and animals. The first reports about a sensitive ra- dioimmunoassay for plasma aldosterone and about a preparation of dispersed zona glomerulosa cells were published in 1970 (Mayes et al. 1970; Haning et al. 1970). These two developments alone turned out to have a tremendous impact on research in aldosterone physiology (for reviews see Coghlan et al. 1979b; J. F. Tait et al. 1980b). In 1971, atrial natriuretic peptides, somatostatin, and the precursor molecule of ACTH had not yet been discovered. Angiotensin antagonists and con- verting-enzyme inhibitors were not yet available. The clinical syndrome of hypo- reninemic hypo aldosteronism was unknown. The possible roles of prostaglandins and dopamine in the control of aldosterone pwduction had not been considered. Cyclic AMP was then the only substance with a clearly established second-mes- senger function.

Reevaluation of tumor classification, differential diagnosis and differential therapy based on modern knowledge. Revision of all chapters to incorporate new facts based on recent discoveries.

Diabetes is now reaching epidemic proportions, and the associated complications of this disease can be disabling and even life-threatening. In Type 2 Diabetes: Methods and Protocols, leading investigators provide up-to-date explanations of commonly used laboratory protocols used in diabetes research. Covering the commonly described in vivo and in vitro model systems, the volume ultimately leads to an overall view of how cellular dysfunction and degeneration leads to susceptibility and diabetes disease progression. Written in the highly successful Methods in Molecular Biology series format, chapters include brief introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and expert notes on troubleshooting and avoiding known pitfalls.

Comprehensive and cutting-edge, Type 2 Diabetes: Methods and Protocols offers succinct, proven techniques to aid research scientists and clinicians in continuing the study of this debilitating disease."

Latest issue in the CURRENT TOPICS IN NEUROENDOCRINOLOGY se- ries which has been gaining a great deal of reputation as a primary source for reviews in neuroendocrinology and related areas in the past few years.