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."

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.

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 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.

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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Even a brief scan of the table of contents of the present volume is enough to disclose the diversity of research interests and opinions in the field of lipidology. It is precisely this diversity that is the strength of our field and that was showcased by the XII International Symposium of DRUGS AFFECTING LIPID METABOLISM (DALM). The papers published here from these proceedings may be divided into three categories: those that define-and refine---our understanding ofthe clinical benefit of aggressive lipid management, those that develop our knowledge of ris!. assessment, and those that discuss the genetic, bio~hemical, and biophysical mechanisms underlying the pathology of coronary heart disease. On the clinical front, further analysis of the results of the Scandinavian Simvastatin Survival Study (4S) has indicated the cost-effectiveness of therapy in patients with established coronary heart disease. The West of Scotland Coronary Prevention Study (WOSCOPS), whose methodology was described at the DALM XII symposium, has demonstrated in a mostly primary-prevention population what 4S demonstrated for secondary prevention the year before: aggressive lipid-regulating therapy reduces coronary heart disease morbidity and mortality rates without concurrently increasing mortality from noncardiovascular causes. In the future, important considerations will be to develop protocols that maximize benefit in groups underrepresented in traditional clinical research for example, women and the elderly-and to improve compliance to existing treatment regimens. Furthermore, antioxidant, omega-3 fatty acid, and gene therapies warrant further investigation.

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.

This volume, The Adrenal Gland, is the second in the Clinical Surveys in Endo crinology series. Like its predecessor on the pituitary gland, this work is written with one purpose in mind-to view the vast, relevant adrenal literature through a clinician's eyes. The intricate, and often complex, interrelationship between the clinical and research perspectives of "adrenology" poses a challenge. This is, in part, due to the commonly held belief that the milieux of steroid hormone research and clinical medicine are parallel phenomena, not destined to meet. But the twain do meet, and often with relative ease, when viewed as twin facets of the same gem. The view presented in this work is from the vantage point of the clinical endocrinologist who applies the research literature to understand adre nal diseases more clearly. Adrenal pathology is arguably the most fascinating of all endocrinopathies. The images of patients suffering from adrenal diseases are of kaleidoscopic quality: the newborn child with ambiguous genitalia, in whom the very first ritual of assigning sex becomes shrouded with uncertainty; the revitalized pa tient with hitherto undiagnosed Addison's disease, who but for the cognitive powers of the endocrinologist would have ultimately succumbed, undiagnosed; the virilized female with adrenal tumor and its attendant onslaught on the body and mind; the febrile patient with pheochromocytoma masquerading as fever of undetermined origin for months."

"Man's natural instinct, in fact, is never toward what is sound and true. It is toward what is specious and false . . . The ideas that conquer the race most rapidly and arouse the wildest enthusiasm and are held most tenaciously are precisely the ideas that are most insane. This has been true since the first 'advanced' gorilla put on underwear, cultivated a frown and began his first lecture tour, . . . " H. L. Mencken, from Meditation On Meditation in the Smart Set, June, 1920 pp 45-46 In our opinion there is no field of clinical medicine in such a state of dynamic disequilibrium as clin ical thyroidology. Thyroid diseases are very common. The moderately complex but easily understandable physiological interrelationships between the thyroid, pituitary and hypothalamus have provided stimuli for the application of mod ern technology in the development of an array of diagnostic procedures. Although therapeutic methods have been more stable, and recent advances more limited, their application by phy- Joel I. Hambufl er. M. D. sicians representing different disciplines has pro vided an ample basis for the expression of differ ing viewpoints. Unfortunately there are few opportunities for in-depth exploration of different attitudes and experience relevant to issues of current interest. The review process employed by medical journals often seems to stifle the expression of controver sial viewpoints."

The first Meadowbrook Symposium was held in 1978 and during the intervening ten years our knowledge concerning how steroid hormones function at the level of gene expression has advanced by leaps and bounds. In this volume, which sum marizes our fourth meeting, these advances are very evident. What seemed like science fiction ten years ago has become commonplace science. Who would have imagined that we could synthesize a nucleotide sequence that binds a specific steroid receptor and acts as a controlling element for gene expression? No one; but as is evident from the results reported in several chapters, this technique is yielding a wealth of information. Using these and other techniques it has become apparent that gene transcription is controlled by interactions between transacting factors and DNA recognition sequences (response elements). These transacting factors appear to be members of a large gene family that includes steroid hormone receptors, transcription factors, protooncogenes and homeobox proteins. Thus a great deal has been learned, but as usual, questions remain. Many of these questions are posed by the findings and observations found in several chapters in this volume. Non hormone binding forms of steroid receptors and their relevance to receptor down regulation, recycling and biological response remain a mystery. The quantitative relationship between receptor binding and biological response still presents agonizing problems. These and many other intriguing questions are discussed in this volume and set the stage for what should be a most rewarding time in endocrinology. Winter 1989 ARUN K."

The XIIth North American Testis Workshop was held in Tampa, Florida, April 13 to 16, 1993. The program consisted of 23 invited lectures and 120 poster presentations. In keeping with the tradition of the Testis Workshop, every attempt was made to emphasize recent develop- ments in the study of endocrine and gametogenic functions of the male gonad. Although the main emphasis, reflected in the title of the pro- ceedings, was on the function and control of somatic cells in the testis, one session was devoted to germ cells and one to the studies of male reproductive development and function. The last session of the workshop was included in the program of the Postgraduate Course of the American Society of Andrology, which held its annual meeting in Tampa imme- diately following the workshop. This volume consists of 21 chapters prepared by the speakers and 8 chapters contributed by presenters of the posters. The Program Committee consisted of Drs. Nancy Alexander, C. Wayne Bardin, Andrzej Bartke (Chairman), Kevin J. Catt, Claude Desjardins, Maria Dufau, Michael Griswold, Norman Hecht, Aaron Hsueh, Dolores J. Patanelli, Bernard Robaire, and Richard Sherins. The workshop was generously funded by Serono Symposia, USA, which also agreed to handle registration, local arrangements, and publication of this volume. On behalf of the Program Committee and all participants, I would like to thank Dr. Bruce Burnett of Serono Symposia, USA and his staff for their efforts and support in every aspect of the organization of the workshop.

Key workers in vascular medicine and biology apply state-of-the-art techniques in cell and molecular biology to study the endothelial and vascular smooth muscle cells. The distinguished scientists and clinicians open a new area of endocrinology, which sees the vasculature and kidney as endocrine organs and sheds new light on the hormonal regulation of the cardiovascular system. They also add significantly to our current understanding of the autocrine, paracrine, and endocrine regulation of vascular function in health and in those vascular disease states that accompany diabetes mellitus, dyslipidemia, and hypertension. Endocrinology of the Vasculature is the first book to comprehensively and systematically explore the vasculature as an endocrine organ.

In this book on diabetes mellitus both the pathogenesis and treat ment of the disease will be discussed. Pathogenetic studies have led to the distinction between type I and type II diabetes. In type I hyperglycaemia is due predominantly to insulin deficiency; in type II insulin resistance is more important. Three pathogenetic factors are thought to play a role in the etiol ogy of type I diabetes: heredity, viral infections and immunity. There may be a relationship between these three aspects since genetic pre disposition changes the susceptibility to viral infections and/or the immunological defence against these infections. Insulitis ensues. Auto immune processes initiated by this chain of events may contribute to the destruction of the B cells in the islets of Langerhans and diabetes -may eventually follow. This means that at the time of the sudden out break of the disease, the destructive process has already been active for years."

From 11 to 15 July 1977 about 60 physiologists, endo crinologists, ecologists and other biologists from 14 countries convened at the University Montpellier for a symposium on Environmental Endocrinology. This meet ing was organized as a Satellite Symposium of the 27th International Congress of Physiological Sciences, Paris, 18-23 July 1977. This volume is a record of the com munications presented at the symposium. The objectives of the program were to examine the role of the endocrine system in a wide spectrum of adjustments and adaptations to changes in environmental conditions by various spe cies of animals, including man, and to promote an ex change of ideas among investigators who have approached these functions from diverse aspects. The diversity of the information and ideas communicated is great. Of necessity, they represent only an extremely modest se lection of the many facets of endocrine function in the interaction of animals with their environments. Be yond the usefulness of the communications individually, we hope that they collectively demonstrate the substan tial heuristic value of the concept of environmental endocrinology as it was perceived by the participants. We acknowledge gratefully the kindness and sympathy of Professor Jaques ROUZAUD, President of the University of Montpellier II, for his generous extension of the hospitality of the University to the Symposium. We are most grateful to Mrs. Monique VIEU who effected so well the secretarial organization of the Sympos."

These four volumes comprlslng "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at a landmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, SwitLerland in February 1988. The Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of The International Commitlee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of fertility and Sterility, The University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US foundation for Studies in Reproduction Inc. , and help from the World Health Organization. B. H. Vickery B. Lunenfeld June 1989 xiii LIST OF CONTRIBUTORS TO THE SERIES A. Abbondante H. Bartermann First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" D-2300 Kiel 1, FRG Rome, Italy M. Bartholomew P. Abel Department of Medicine/Endocrinology Department of Urology Milton S. Hershey Medical Center Hammersmith Hospital Pennsylvania State University DuCaneRoad PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck H.

Tamoxifen has persisted as a widely accepted and administered drug for almost 25 years. Following the many scientific papers and books on the subject, it has remained a very intriguing substance. This, perhaps, is the reason for another monograph on Tamoxifen. It is regrettably true that overviews, even when up to date after exhaustive research - the shibboleth of our cultures -, rapidly lose relevance with the passage of time. Scientists can sometimes be pictured as deep sea divers, who plunge into the unknown in search of a hitherto unknown world. Their descent is exciting, but eventually they must come up for air and integrate their experiences with others who also had to resurface. This book intends to collect and, where possible, to collate recent, but sometimes seemingly unrelated information. To quote Stephane Mallarme: "Everything in the world exists to end up in a book." Even if this is a tad cynical, it might not be far from the truth. If a little knowledge is a dangerous commodity, one can also add - tongue in cheek - that a vast amount of knowledge can be truly hazardous. It is likely that what might seem as entangled data is confusing, especially for those satisfied with the comfortable interpretation of Tamoxifen as an antiestrogen which has long been found insufficient. The complexity of its mechanisms and effects defies simple explanations and may even seem capricious, but only because of our ignorance.

The subject of this book is neuroendocrinology, that branch of biological science devoted to the interactions between the two major integrative organ systems of animals-the endocrine and nervous systems. Although this science today reflects a fusion of endocrinology and neurobiology, this synthetic ap proach is relatively recent. At the beginning of the 20th century, when the British physiologists, Bayliss and Starling, first proposed endocrinology to be an independent field of inquiry, they went to great lengths to establish the autonomy of chemical secretions in general and their independence from nervous control in particular (Bayliss, W. M. , and Starling, E. H. , 1902, The mechanism of pancreatic secretion,]. Physiol. 28:325). They argued with Pav lov, who said that there was a strong influence of the nervous system on the gastrointestinal phenomena the endocrinologists were studying. For several decades, the English physiologists prevailed, at least in the West; and Pavlov's critique was not taken to heart by the practitioners of the newly emerging discipline of endocrinology. Through the work of Harris, the Scharrers, Sawyer, Everett, and others, there has been something of a scientific detente in the latter half of this century; the hybrid field of neuroendocrinology is now regarded as one of the corner stones of modern neural science and is of fundamental importance in basic and clinical endocrinology.

In 1980 a case of myxedema was treated in Lisbon by the implantation of a sheep thyroid gland with the immediate improvement in the patient s condition. A few years later, medications for the then ill-explained condition of the menopause included tablets made from cow ovaries. In the first quarter of the 20th century the identification vitamin D3 and its sunlight driven production in skin paved the way to the elimination of rickets as a major medical problem. Twenty years or so later Sir Vincent Wigglesworth established the endocrine basis of developmental moulting in insects, arguably the most commonly performed animal behaviour on Planet Earth. A paradigm that would unify these disparate observations arose between in 1985 and 1987 beginning with the identification of the glucocorticoid receptor and the nuclear receptor super-family. What follows is a timely and positive manifestation of the capacity, productivity and value of international human scientific endeavour. Based on intrigue, lively competition and cooperation a global effort has rapidly fostered a school of biology with widespread ramifications for the understanding of metazoan animals, the human condition and the state of the planet. This book is the first this century to try and capture the spirit of this endeavour, to depict where the field is now and to identify some of the challenges and opportunities for the future. "

The conference represented by this book was made possible by support from NICHD and a planning committee headed by Dr. Richard Sherins. Two general areas of research are included: the first encompasses steroid hormone synthesis, metabolism and transport in the testis; and the second relates to hormonal regula tion of the seminiferous tubule with special emphasis on the con trol of Sertoli cell function. In addition, there are sections on the purification of unique testicular proteins and morpho logical studies with particular emphasis on the Sertoli cell. We would like to express our sincere thanks to Dr. Sherins and his staff at NICHD and to all of the people at the University of North Carolina who participated in the Conference arrangements, to Dr. Judson J. Van Wyk, Chief of the Pediatric Endocrinology Division, and Dr. H. Stanley Bennett, Director of the Laboratories for Reproductive Biology. Our very special thanks to Mrs. Carolyn Jaros for her help in handling the local arrangements. Mrs. Martha Byrd and Mrs. Linda Rollins typed the manuscripts. Miss Leslie Wells and Mr. Albert Smith kindly assisted in proof reading, and Dr. Elizabeth Wilson gave much help with the final editing process. To all of these people, we are most grateful."

Three years ago, most authors contributing to this book gathered at the Heinrich Fabri Institute of the University of Tubingen at Blaubeuren near Ulm in Germany for the third conference on "Pineal Gland and Cancer." In 1987, the late Derek Gupta organized the second meeting and published the first book on the topic, 10 years after Vera Lapin, as part of the 25th anniversary celebrations of the Vienna Cancer Research Institute, had held the first meeting. It was in Vienna during the 1930s and 1940s that W. Bergmann and P. Engel demonstrated that pineal extracts possess growth inhibitory properties on experimental rodent tumors and R. Hofstatter reported favorable results when these extracts were given to cancer patients. In the 1970s, Vera Lapin and others reported that surgical removal of the pineal gland (pinealectomy) stimulates experimental tumor growth rendering fundamental support for an involvement of the pineal gland in malignancy. A focal question of past and present research in this field is whether the pineal gland exerts its tumor inhibitory activity primarily or exclusively via melatonin. Currently, it appears that the action of melatonin on experimental tumor growth criti cally depends on the circadian timing of its administration as weH as on the type and stage of cancer, and that primarily highly differentiated tumor ceHs are controHed. Initial clinical applications of the pineal hormone for incurable cancers raise hopes for a promising future use, particularly when combined with other therapies (e. g."

"Endocrine Pathology" integrates classical diagnostic anatomic pathology with recent developments in immunochemistry and molecular biology in its approach to endocrine disorders. The book discusses not only a wide range of diseases commonly encountered in everyday clinical practice but also those uncommon conditions elucidated by such innovative techniques as ultrastructural immunochemistry and in situ hybridization.

CHARLES Y. c. PAK Major progress has been made in the pathophysiologic elucidation and management of nephrolithiasis during the past two decades. It is now possible to detect the cause of stone disease in more than 95% of patients, to prevent recurrent formation of stones in the majority of patients, and to remove most existing stones less invasively. The assumption of editorship of this book permits me to indulge in the discussion of this progress from my personal perspective. Three somewhat fortuitous events in my academic career dictated my directing major efforts in stone research. The first event occurred in 1963 when, after having completed medical training, I was faced with two years of military service as a participant of the Berry plan. Choices were limited and disconcerting for someone interested in a research career: a staff physician at a military installation or an indian reservation, or a member of a research team in a state penitentiary. An interesting article by Norman Gershfeld on phospholi pid monolayers prompted me to write him seeking a position in his laboratory of Health (NIH) in Bethesda, MD. Partly because of at the National Institutes my rudimentary exposure and publication in surface chemistry, I was offered a position as a staff scientist and a position in the Public Health Service which satisfied the requirements of a military service."

This book is made up of 16 papers delivered during the Paediatric Conference convened by the Royal College of Physicians of London on 20th and 21st October 1983. The main intention of the conference was to allow each contributor to deliver a personal review of his own field, indicating recent develop ments and current practice. This volume, representing the proceedings of that meeting, is not intended as a comprehensive textbook of paedi atric endocrinology but rather as a series of personal narratives. I wish to express my thanks to the Chairmen, who so ably stimulated discussion, and to Miss Gillian Andrew, Conference Secretary of the Royal College of Physicians, and her colleagues, for providing invalu able help in the organization of the conference. I am also grateful to the staff ofMTP Press Limited for their help in producing the book. A. Aynsley-Green IX LIST OF CHAIRMEN Professor R. Hoffenburg PRCP Dr D. I. Johnston MD FRCP President Queen's Medical Centre Royal College of Physicians Nottingham London Dr D. A. Price FRCP Royal Manchester Children's Professor J. W. Farquhar MD FRCP(Ed) Hospital Department of Child Life and Health Pendlebury University of Edinburgh Manchester Edinburgh Dr P. H. W. Rayner FRCP Dr C. C. Forsyth MD FRCP Institute of Child Health Department of Child Health University of Birmingham University of Dundee Birmingham Dundee x LIST OF CONTRIBUTORS Dr D. B. Grant MD FRCP Dr J."

Polycystic ovarian disease, or polyfollicular ovarian disease, as Dr. Fut terweit prefers to call it, is a disease of uncertain etiology and for which numerous modes of therapy have been advanced. Understanding of its pathophysiology should shed light on factors regulating normal ovarian function; the converse is also true. Recent years have brought about great understanding of the neuro endocrine regulation of gonadal function, as well as of factors in the microenvironment of the ovary which affect its function. It is also ap preciated that cases classified as polycystic ovarian disease actually rep resent a clinical and pathological spectrum which may reflect the effects of diverse etiological factors. In the present volume, Dr. Futterweit presents the fruits of his long interest in and extensive experience with this disease. He thoroughly and thoughtfully reviews the vast amount of basic and clinical information that has been garnered with regard to this condition over the past decade. The numerous theories that have been advanced to explain its etiology are presented in balanced fashion, in addition to a hypothesis, which is well formulated and amenable to clinical testing. His clinical interests and judgment are well represented by his presentation of the diverse manifestations of this condition, the approach to proper diagnosis, and the available therapeutic options. Patients with this disease represent diagnostic and therapeutic prob lems in a situation where manifestations of disease may lead to major emotional stress."

This volume describes the proceedings of the Workshop Conference on The Human Testis which was held at Positano, Italy, April 23-25, 1970. The format of the book has been arranged according to topics discussed during the Conference. Each chapter includes individual contributions followed by discussion. Thus, this volume provides a current critical evaluation of the subjects discussed. The Editors assume responsibility for any shortcomings and wish to thank all par~ ticipants for their unprecedented cooperation in making this publi cation possible. The Editors are indebted to Miss Barbara Martin for her able secretarial and administrative assistance and to Mrs. Griff T. Ross who supervised the secretarial staff during the conference. Rec ognition is also due to Mrs. M. Flack for editorial assistance. The Workshop Conference could not have taken place but for the Serono Foundation, which supported this Meeting as well as the pub lication of the Proceedings of this Workshop. The physical as well as the technical arrangements were under the careful direction of Mr. Cesare Florimonte of the Serono Foundation. The support pro vided by the Serono Foundation is another proof of its generosity in stimulating scientific exchanges and a demonstration of its con tinuous efforts to support basic and applied studies in the field of human reproduction. We express our thanks to our Publisher, Plenum Press, for their fine cooperation and for ensuring the rapid publication of this vol ume.