The field of human artificial reproductive technology (ART) is continually advancing and has witnessed significant changes since the inception of Louise Brown in 1978. Though Louise Brown herself was conceived after the trans fer of a blastocyst, there remain significant confusion and debate regarding the stage at which the human embryo conceived in the laboratory should be replaced in the mother. Developments in culture media formulations, leading to the introduction of sequential media, have brought the role of the blasto cyst in human ART back into the spotlight. It was due to this resurgence of interest in the niche of extended culture in human infertility treatment that the symposium on "ART and the Human Blastocyst" was held. of this meeting within this volume bring to the forefront The proceedings the main issues raised with the transfer of embryos at the blastocyst stage. It is evident from the chapters that follow that ART needs to be perceived as a continuum of procedures, each one dependent on the preceding one, and all equally as important as each other. That is to say, the development of a com petent embryo is ultimately dependent on the quality of the gametes from which it was derived. With regard to the oocyte, this then places the emphasis on the physician to use a stimulation protocol that both produces quality oocytes and does not impair endometrial function. Maintenance of gamete and embryo quality is the laboratory's role.

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.

The evolution ofdata about the HIV-Associated Lipodystrophy Syndrome has been rapid. The syndrome itself is complex and controversial. Although great progress has been made in understanding epidemiology and etiology of the syndrome, much about the syndrome remains mysterious. It was our intention to assist HIV providers with a framework for understanding the status and complexities ofthe field. Each author was requested to provide an evidence-based discussion of a topic for which they have expertise. While it is impossible that such a volume be completely comprehensive, we believe that the approach of this book will allow the reader to develop a relatively complete snapshot of the syndrome. We also believe that the reader of this volume will be able to confront the emerging literature on the HIV-associated lipodystrophy syndrome with a critical eye and that the volume will provide a context in which to place additional data as they are published.

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.

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.

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.

Fresh insights into the pathogenic mechanisms by which hyperglycemia induces tissue and organ injurt are the basis for rapidly evolving promising therapies in diabetes. Especially promising as targets for intervention are products of oxidative stress, including kinins and growth factors. Improving results of renal replacement regimes now incorporating pancreatic islet transplants are able to delay and prevent end-organ damage in diabetic individuals. The evolving story of the taming of diabetes is of direct concern to nephrologists, endocrinologists, ophthalmologists, primary care physicians and medical students.

The Fifteenth Midwest Conference on Endocrinology and Metabolism, held at the University of Missouri-Columbia on October 11 and 12th, 1979, hosted the most prominent active researchers in the world on the subject of the hormone relaxin. Each speaker presented an in-depth coverage of his chosen topic and area of expertise. Some of the data presented in this book are findings which have not been pub lished in a scientific journal. The topic of this conference is especially timely in light of the fact that this is a first confer ence devoted specifically to the hormone relaxin. Progress on this hormone has been exceedingly rapid in recent years and many signif icant breakthroughs are documented in these pages. Lively discus sions following each presentation attest to the enthusiastic research effort being pursued at the present time concerning relaxin. Traditionally the Midwest Conferences on Endocrinology and Metabolism have emphasized breadth as well as depth of coverage. The present Conference has covered the many active areas of research in relaxin, including morphological aspects of the hormone's origin, chemical purification and chemical structure, bioassays, radioimmuno assays, receptors, mechanism of biochemical action and physiological responses to the hormone. Advances in relaxin were slow since its discovery by Dr. Frederick Hisaw, Sr. in 1926 until the availability of homogenous preparations some seven years ago. In the suceeding seven years, activity in the subject has accelerated remarkably."

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.

The past two decades have witnessed an unprecedented growth in the field ofneuroendocrinology. The conjoint research contributions by clinicians and basic scientists have promulgated revolutionary concepts at a breakneck speed. This first volume in Clinical Surveys in Endocrinology, The Pituitary Gland, has been written with but one purpose in mind: to integrate the current knowledge in this dynamic field with the existing body of information already available to the clinician. The chapters in this book attempt to portray current research information seen through the eyes of a clinician. The contributions of pioneers in each field have been placed in a perspective relevant to the practicing endocrinologist. The selection of the almost 1500 references from a bewil of literature has been inftuenced by the degree to which these dering body articles-original as weil as review papers-contributed to the growth of pi tuitary endocrinology. Despite the most scrutinizing attempts, it is inevitable and regrettable that works of importance must be excluded due to the practical limitations of any comprehensive work. Nevertheless, to the researcher these references are complete enough to serve as a significant resource. To the reader who wishes to gain an indepth clinical perspective of pituitary disor ders, this work is written precisely from that vantage point. The single authorship of this work notwithstanding, several friends have been instrumental in the completion of this work. I deeply appreciate the incessant zeal and excellent assistance of Ms."

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."

Early embryonic loss is a continuing social and economic global problem. In human populations the estimates of interruptions early in pregnancy range from 35-60%. In animal husbandry (swine, ruminants) fully 30% of pregnancies fail to survive early events of gestation. The futility associated with this persistant high risk is even more unsettling because of advances made in assisted reproductive technology which, although this very selective methodology has added to our knowledge of embryo-endometrial interactions, has resulted in a birth rate of only 14%. These studies have instigated comparisons of the live relative contributions of the embryo and the uterus to the outcome of pregnancy. These analyses have shown that we have learned significantly less about the role of the uterus in deciding the outcome of either natural or assisted pregnancies. In 1979 a quotation by George Corner was used to set the tone of a meeting that was devoted to discussion of the cellular and molecular aspects of implantation. In spite of the proliferation in research activity which occurred in the following 15 years our real understanding of the embryo transfer process has fallen short of our expectations. We use the Corner quotation, once again, to preface this symposium so that we may recall that the fundamental nature of the process which regulates embryo-endometrial interactions still escapes us.