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.

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."

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

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.

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.

When new fellows join my lab, I give them some reading materials so that they can orient themselves in their assignment in a new eld. When fellows leave my lab, some after writing their dissertations, I prefer to give them a book as a symbolic present. I was longing for a book that contained something on more or less eve- thing about the islets. At the same time, I wished it contained information as recent as possible. There are a few such books in the market but they are pretty outdated. I started picking islets myself from October 1990, when I joined the Rolf Luft Center, Karolinska Institutet. Over the years my fascination for islet research remained high. Since last year, I felt a stronger urge to do more for these mysterious and hidden mini-organs that are directly or indirectly involved in the pathogenesis of all forms of diabetes that affects ?250 million people in the world. After I launched the Islet (landesbioscience. com/journals/islets) and founded the Islet Society (isletso- ety. org), there was a momentum that could be utilized to create something equally meaningful i. e. this book. The idea cracked in September 2008. Starting September 19, 2008, I contacted an estimated 90% of the authors who published anything on the islets during 2007-2008 and who could be traced from the internet.

This book is divided into two main sections, and covers a broad range of issues important for health practitioners to be aware of when caring for people with co-morbid diabetes and depression. Section One of the book contains the overall ideas and the more recent developments in measuring psychological morbidity in people with diabetes. When attempting to identify people with depression or other psychological problems, it is important for practitioners to recognize the limitations of screening as well as its utility. Issues such as the basic principles regarding when and when not to screen, the cultural applicability of tools, different questionnaire formats and key concepts such as sensitivity and specificity of tools, and their positive and negative predictive value, will be considered. In particular there has been increased interest in the concept of diabetes-related distress and several tools have been developed to measure this. There are broad-based measures of distress such as the Problem Areas in Diabetes (PAID) scale, the Diabetes Adjustment Scale (DAS), The Diabetes Health Profile, The Fear of Hypoglycemia Scale, etc. There are also a range of generic quality of life tools which have been used effectively in people with diabetes; for example the Medical Outcomes Survey Short-Forms (SF36, SF12), the World Health Organisation Well-being questionnaire (WHO-5) and the EQ5-D. These tools are important because they measure aspects of psychological well-being that are specifically associated with the experience of having a long-term conditions and so have important implications for both self-care and health care practice. The potential overlap of symptoms of depression and symptoms of diabetes-related distress are considered in this section and the implications for practice discussed. Section Two covers the most commonly used tools that have been used to screen for depression. For each tool considered some information which is easily referred to by the readeris set out in a table which includes details of the authors, time of first use, country where it was first developed, some examples of the questions used, the languages it is available in, data on sensitivity/specificity. Each instrument will then be discussed in terms of its use in research as well as practice, and its applicability in different patient groups, different cultural settings and so on. Guidance on the practical use of each tool is included, and the most popular depression screening tools are focussed on.

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."

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."

In the first section of this volume, we have attempted to bring together some of the papers that reflect exciting new areas of development in relation to neuroendocrine investigation. Very recently, specific nucleotide recognition sequences for thyroid hormones, steroid hormones and the fundamental intracellular regulator, cyclic AMP, have been determined. In this section, the preliminary characterization and investigation of the nuclear binding proteins that mediate the actions of cAMP are described. Not only does this represent an important advance in cell biology, but it may represent a further level of alteration in control in normal and disease states. Intercellular pituitary "cross talk" is well described in the in vitro setting. The active molecules are clearly It is now important able to exert significant actions at the subnanomolar level. to design experiments in order to define the precise physiological relevance of these novel and potentially important observations. Paracrine and autocrine cellular interactions are of established importance in growth control in a variety of body tissues. But it is only very recently that the investigation of normal and abnormal anterior pituitary growth has reached the forefront of neuroendocrine research. This is perhaps surprising, beause the inhibitory effects of doapmine agonism on lactotroph growth and differentiation have been appreciated for some time. The anterior pituitary gland produces numerous growth factors that exert a variety of functional effects on pituitary hormone synthesis and release.

A lot of time has been spent trying to convince health care providers and policy makers of the enormous importance of macrovascular disease in persons with type 2 diabetes. In this volume, we present facts that dem onstrate how important it is to recognize macrovascular disease in these patients in daily practice. This volume has been compiled to help those already involved in dia betes care, to be more involved in cardiovascular risk control, a task that is not easily achieved. The area of cardiovascular risk in type 2 diabetes is heterogeneous. Trying to characterize it, we can only say: certainly we know more than we do, but for sure we do less than we could. Our challenge is to change this. Nicolae Htmcu Professor N. Hancu was born in Romania in 1940. He studied medicine at the Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, and obtained his speciality in internal medicine in 1970, and in diabetes, nutrition and metabolic disease in 1986. He was appointed Professor and Head of the Department of Diabetes, Nutrition and Metabolic Diseases of the same university in 1993. He has been a full member of the Romanian Academy of Medical Sciences since 1995. Professor Hancu's major interest is related to clinical lipidology, visceral obesity, and cardiovascular risk in type 2 diabetes. He has published over 200 papers and 14 books in this area. He has been invited as Visiting Professor at many universities in Madrid, Valladolid, Barcelona, and Los Angeles.

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."