Changes in the allocation of healthcare resources have raised issues related to the efficacy and outcomes of medical therapy and how such factors may be measured. The questions associated with the quality of life and functional capability of patients with chronic health conditions have been of special interest. Endocrine disorders have the potential for disrupting the general health and well-being of affected individuals and their families; thus they warrant serious attention. This symposium was convened in November 1997 at Palm Beach Gardens, Florida, to bring together medical, behavioral, and social scientists. The meeting fostered the presentation and discussion of the most current clinical research on the effects of various therapies on a wide range of endocrine disorders from diabetes to adrenal insufficiency and growth hormone deficiency. The participants, all noted national and international experts in their fields, focused their attention on both the biomedical value and effectiveness of treatment, as well as on the impact such treatments have on psychological states such as mood and cognition. Many presentations specifically emphasized the quality of life (QOL) indicators that now regu larly appear in many research protocols and reports. The pioneering work of two clinical researchers was a major highlight of the meeting and an Award of Recognition was presented to Robert Blizzard, M. D. , and John Money, Ph. D. , for their innovative and insightful work in pediatric endocrinology and psychosexual development.

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.

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."

The epididymis has great significance in the reproductive biology of the male and it is gaining recognition as an organ worthy of study in its own right - where the secretory and absorptive activities of one tissue (the epithelium) profoundly modify the function of another (the spermatozoon). Apart from cases of epididymal agenesis or physical blockage, however, it is not yet known to what extent mal functions of the epididymis contribute to "unexplained" male infer tility, but its importance as a target for antifertility agents in the male is now widely appreciated. This monograph evolved from two lectures on epididymal func tion given at the National Research Institute for Family Planning, Beijing and the Sichuan Provincial Family Planning Research Insti tute, Chengdu, China in 1983. In order to stress for this audience the central importance of the epididymis in fertilisation, and so highlight its potential for attack by antifertility agents, the talks attempted to put the epididymis in reproductive perspective by stressing the func tional development of the sperm cells during their sojourn in the epididymis, rather than merely listing the changes observed in them."

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.

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.

Since the first description of Philadelphia chromosome-negative chronic myeloproliferative disorders more than 100 years ago, the diagnosis and therapy of these conditions have been based primarily on clinical experience and judgement. Until recently very little was known about the molecular basis of these diseases. In order to spark research in this area basic scientists and clinicians from various parts of the world have contributed to this volume, the first of its kind to put together the current knowledge. The book deals with the new WHO classification of these disorders, novel aspects of diagnostic pathology, the search for disease-relevant genes utilizing molecular biology and proteomic techniques, the description of the roles of PVR-1 and VHL genes for polycythemias and the discovery of the gene mutation responsible for the idiopathic hypereosinophilic syndrome. A chapter on anagrelide, an important novel drug for the treatment of primary thrombocythemia, is included.

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.

Lactogenic hormone activity was first observed in bovine pituitary extracts by Stricker and Griiter in 1928, working in Bouin's laboratory in Strasbourg. Since that time prolactin has been shown to exist in anterior pituitary extracts of almost all vertebrate species investigated. Although its biology was extensively studied in many mammalian species, the existence of prolactin in the human was generally doubted, despite the positive evidence produced by such researchers as Pasteels. This can partly be explained by the fact that human growth hormone isolated in 1961, is itself a potent lactogen, in contrast to nonprimate growth hormones, and is present in the normal human pituitary in much greater amounts than prolactin. As a result there was a lag of nearly 10 years until prolactin was unanimously accepted as a hormone of the human pituitary, separate from human growth hormone. In 1970 new bioassay techniques permitted the demonstration of prolactin bioactivity in the serum of postpartum women and galactorrhea patients, and chromatographic methods led to the isolation and purification of human prolactin allowing the establishment of a specific radioimmunoassay for this hormone. This opened the road to the understanding of prolactin physiology and pathophysiology in the human, which has revolutionized clinical neuroendocrinology and reproductive endocrinology. Particularly hyperprolactinemia has turned out to be one of the most common endocrine syndromes.

This book was written at the invitation of Dr. H. GOTZE of Springer-Verlag for the series "Monographs in Endocrinology." It is not a comprehensive account of the prostaglandins but has been writ ten with a deliberate emphasis upon those aspects of the field in which I am particularly interested and to which, in some cases, I have made a contribution. I am grateful to Miss E. PFISTERER and her colleagues of Springer Verlag for their excellent work. I should also like to thank my wife without whose patience, encouragement and help this book would never have been completed. Finally this is an appropriate time to express my sincere gratitude to those scientists who over the years have given me samples of prostaglandins-namely Professors S.BERGSTROM and B.SAMUELSSON of the Karolinska Institute, Stockholm, Professor D. A. VAN DORP of the Unilever Research Laboratories, Vlaardingen and Dr. J. E. PIlm of the Upjohn Company, Kalamazoo. Without their help work in this field would have been extremely difficult."

Recent advances in molecular biology have provided new dimensions in the study of the reproductive system. There has been major progress in our understanding of the molecular mechanisms of hormone action in the past few' years. The symposium on "Molecular Basis of Reproductive Endocrinology" was organized to highlight new research findings on the regulation of the hypothalamic-pituitary-gonadal axis. The emphasis of the symposium was on physiological questions answered by the molecular biology approach. Studies on the functional relevance of gonadotropin releasing hormone and LH and FSH gene expression were presented, together with research on the molecular biology of ovarian and testicular steroidogenic enzymes and protein hormones. Also, several novel aspects of hormone gene expression in placental tissues were reviewed. The symposium was held July 25 to 26, 1991, immediately prior to the 24th Annual Meeting of the Society for the Study of Reproduction, on the campus of the University of British Columbia in Vancouver. Serono Symposia, USA generously financed and coordinated the meeting. We are indebted to Dr. Bruce K. Burnett and Dr. L. Lisa Kern for their professional assistance in the organization of the symposium. We would also like to thank Drs. Victor Gomel, Basil Ho Yuen, and John Challis, who served as session moderators. Most of all, we truly appreciate the efforts of all the invited speakers, poster presenters, and discussants in making this a memorable event as the largest one-day meeting of the Serono Symposia USA, series.

The physiology and metabolism of thyroid hormones were areas of intense research investigation during the 1970s. Radioimmunoassays were applied to study the concentration of iodothyronines in biologic fluids. These techniques proved to be highly sensitive, specific, and reproducible as well as rapid. The availability of specific radioimmunoassays led to the detection of several iodothyronines in human biologic fluids, e. g., reverse triiodothyronine (rT 3), diiodothyronines, monoiodothyronines, and acetic acid derivatives of thyroxine (T 4) and T 3, which were previously either unknown or briefly considered but forgotten in the 1950s. This monograph is intended for readers who desire an overview of thyroid hormone physiology as it was understood in 1979. It should be especially useful to trainees in endocrinology and individuals interested in potential research projects. The main focus has been on the studies conducted between 1969 and 1978, alt lOugh other information has been reviewed to provide an overall working knowledge of the field. A list of over 500 references, although probably still incomplete, should lead a reader to at least a few important articles in each area relevant to thyroid hormone physiology.

As far as we are aware, this is the first attempt to cover the com parative physiology of the pancreatic islets in a monograph. The topics discussed would probably have sufficed to fill about half a dozen monographs, a matter that becomes obvious from a look at the Contents. Hence, we have tried to present the ma terial more in the form of a digest, to emphasize evolutionary perspectives, to point out critical issues, and to identify challenging topics for future research. This approach required an arbitrary reduction of the num ber of references, and we therefore join the chorus of recent authors who beg their colleagues for understanding if some of their publications do not appear in the bibliography. Keeping up with the current literature was like fighting one of those monsters that grow a couple of new heads for each one that is cut off. Nevertheless, we hope that we have covered most of the key publications up to the autumn of 1986. We gratefully acknowledge the advice of many colleagues, and in particular the invaluable criticisms of Robert L. Hazelwood and Erika Plisetskaya. Special thanks are due to the series editor, Donald S. Farner, for his patience and guidance, both of which were fresh proof of his legendary diplomatic skills. Finally, we wish to thank Dr. D. Czeschlik and his staff at the Springer Verlag for their patience and support. Philadelphia, PA AUGUST EpPLE Greenville, NC JACK E. BRINN September 1987 v Contents Chapter 1. Introduction .......................... ."

The building of conceptual models is an inherent part of our interaction with the world, and the foundation of scientific investigation. Scientists often perform the processes of modelling subconsciously, unaware of the scope and significance of this activity, and the techniques available to assist in the description and testing of their ideas. Mathematics has three important contributions to make in biological modelling: (1) it provides unambiguous languages for expressing relationships at both qualitative and quantitative levels of observation; (2) it allows effective analysis and prediction of model behaviour, and can thereby organize experimental effort productively; (3) it offers rigorous methods of testing hypotheses by comparing models with experimental data; by providing a means of objectively excluding unsuitable concepts, the development of ideas is given a sound experimental basis. Many modern mathematical techniques can be exploited only with the aid of computers. These machines not only provide increased speed and accuracy in determining the consequences of model assumptions, but also greatly extend the range of problems which can be explored. The impact of computers in the biological sciences has been widespread and revolutionary, and will continue to be so.

For many years now I have devoted much of my time to lecturing and writing on the subject of cardiovascular disease (CVD). In this book I have outlined the development of my approach to this problem. I must admit that the details of my theories have undergone continuous modification as a result of the lessons learned in treating a large number of patients, but the basic message has remained the same. I believe that the delay in the utilization oftestosterone treatment for CVD has arisen from a failure by specialists in endocrinology, biochemistry, physi ology, and cardiology to understand each other's point of view and therefore to effectively coordinate their clinical efforts. This is like four people starting to climb the various faces of a pyramid, unaware of each other's presence until they reach the apex. It is hoped that bringing specialists in these different disciplines together at "summit meetings" will help them discover the true nature of this disease, the cardiovascular specialist understanding the underlying lack of anabolic steroids, and the other three grasping the way in which treatment with these compounds can effectively counteract the metabolic disturbance which is the cause of CVD. Even apart of the language barrier, writing this book has by no means been an easy task. Please consider my situation; one cannot be a cardiologist, endocrinologist, biologist, biochemist, and physiologist all in one person. This fact may open me to criticism.

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."

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."

In the past 10 years hirsutism has been the object of a considerable number of fundamental studies. It provides endocrinologists with an experimental model for the investigation of androgen secretion, metabolism and mechanism of action. Plasma androgen assay, free testosterone measurement, hepatic and extrahepatic androgen metabolic clearance and androgen metabolism in the skin are the different steps which were studied by many groups and represent valuable parameters of the mechanisms of hirsutism. Determination of the origin of androgen oversecretion has become easier by technical progress in differential effiuent venous catheterism, which makes it possible to compare androgens in adrenal or ovarian effiuent veins to their peripheral levels, and to determine the ovarian or adrenal source of the androgen oversecretion as well as the side responsible, essential in the case of tumors. The study of androgen metabolism and the discovery of androgen receptors in the skin confIrm the latter as an actual target cell for androgens. This target cell uses the circulating active androgen, i. e., testosterone and can also metabolize local inactive androgens into active ones. This is the case of androstenedione and dehy droepiandrosterone which are the two main androgens secreted in women, since women secrete very little testosterone. The capacity of the skin to transform inactive androgens into active ones varies from one individual to another. That would support the concept of variable skin receptivity from one woman to another and from one ethnic group to another."

This monograph brings together our work concerning the relationships be tween the hypothalamus, pituitary and testis. The studies span approximate ly a decade of collaborative work. Over this period our contributions and those of many others have advanced greatly our understanding of many aspects of male reproductive biology. This monograph attempts to survey these developments and to highlight many unresolved issues. It also provides an opportunity to demonstrate the value of investigations which relate bio chemical to structural parameters and to illustrate the importance of animal studies in elucidating biological principles with clinical applications. The reverse is also important since the pathophysiology of human disorders of ten provides insight into hitherto unsuspected basic mechanisms. In any rapidly expanding field it is difficult to stop revising and extending a manuscript. It is equally difficult to quote every reference in the field but we trust that those of significance have not been omitted. Some of our former students have collaborated with us as co-authors in producing this monograph. It is equally important to recognise the contributions of our other former students and colleagues who have physically participated in the studies and without whose intellectual contributions a number of concepts would not have been elucidated. Their work is acknowledged in the text of the monograph and the extensive list of references."

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."

The field of steroid hormone action has continued to expand into the realm of molecular biology at a pace even faster than most of us ever imagined. techniques of molecular biology have made it possible to clone The hormone-regulated genes and to examine steroid-receptor interactions with these genes. Nucleotide sequences of these genes, which show preferential binding of steroid receptors, have been identified. These results are complemented by the identification of chromatin acceptor proteins, which also show preferential binding for steroid-receptor complexes. Thus, one can envision the day when cloned genes, purified acceptor proteins, and receptor-steroid complexes will be recombined in vitro to form a functional unit. Cellular localization of steroid receptors has undergone recent revision, and it now appears that receptors are localized primarily in the nuclear compartment. These findings, although controversial, will lead to a reassessment of many of the previous concepts of steroid-receptor interactions and regulation. The way in which these observations at the of physiology, molecular and cellular levels fit into the overall scheme development, and evolution are continuing to progress, and the future promises some very exciting syntheses of understanding at all levels of biological organization. The third Meadow Brook Conference on hormones was held in order to bring together investigators who will undoubtedly contribute heavily to this future synthesis and to permit a free exchange of ideas and concepts as they relate to the current state-of-the-art in molecular endocrinology. Spring 1986 ARUN K. Roy JAMES H. CLARK Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Experts in the field of endocrinology as well as ophthalmologists, oncologists, orthopedists and oral surgeons discuss the nature and mechanism of action of growth-stimulating substances whose biological and clinical activities in humans have been demonstrated or are being investigated. The monograph represents a good sampler of current basic and applied knowledge in the field.

The role of electrical signalling in the control of endocrine secretions by the brain has been clear for many years. Recently, the influences of hormones on synthetic events in neuroendocrine cells have raised new questions concerning the peptides released from such neurons. This volume concentrates on the relation between these two fields and asks how electrical action potentials facilitate secretion of substances from nerve cells which control endocrine events. While stimulus-secretion coupling has been studied extensively in other physiological contexts, this is the first treatment of the phenomenon in an exclusively neuroendocrine setting.

In vitro fertilization has resulted in an estimated 4000-5000 births in the world. The procedure has been accepted in Europe, America and Australia and several hundred IVF clinics are operating successfully. The newer procedures of GIFf, embryo freezing and donor oocyte IVF have become established and are dealt with in several chapters. GIFf has become the procedure of choice for patients with infertility of unknown origin. Oocyte freezing represents an important new technology which is being developed. The routine IVF procedure has improved slightly; variation in results can be reduced by quality control of laboratory and clinical techniques. Male factor infertility has been dealt with by IVF in mild and moderate cases, but newer techniques will be required to deal with severe problems in the male. Most countries have accepted that the straightforward IVF pro cedure is ethical. Limitations concerning the use of donor oocytes and embryo experimentation exist in some religions and countries; legal control of the new reproductive technologies ranges from the passage of statutes to no control at all. Many countries are still considering the need for legislative control. The text endeavours to indicate new areas of importance and to guide those organizing services as to how to introduce newer technolo gies.

Conceptual advances in the biological sciences are marked by the applica tion of new techniques and experimental strategies. Nowhere has this ge neric principle been more apparent than in the study of testicular cells, as judged by the evolution of themes presented at the Testis Workshop over the past 23 years. Like its predecessors, the 1995 Testis Workshop was structured to offer fresh insights and approaches for understanding the mechanisms of spermatogenesis and steroidogenesis. The chapters pre sented in this book emphasize three aspects of testicular cell function: first, the molecular analysis of the cell cycle; second, examination of the cell cycle, including the function and identification of specific macromolecules that direct the proliferation and differentiation of germ cells; and third, the development of Leydig cells and the role of specific macromolecules in the formation of testicular steroids. Each chapter is based on a lecture presented at the XIIIth Testis Work shop held on March 30 to April 1, 1995, at the Radisson Plaza Hotel in Raleigh, North Carolina. The selection of topics reflects the recommenda tions of the workshop'S organizing committee. Sincere thanks are due to the speakers who agreed to lecture and prepare chapters."