The Eleventh Midwest Conference on Endocrinology and Metabol ism in September 1975 brought together a number of leading invest igators in the areas of steroid, peptide, acetylcholine, and cate cholamine hormone receptor studies. This book is based upon the reports of investigations into hormone receptor biochemistry and physiology presented at the Conference as well as on the ensuing discussions. However, many of the manuscripts were written after the Conference. Because of this, the reader will find that some literature references and results of i vestigations are more up to-date than the Conference date would suggest. Perusal of this and previous volumes will attest to the high quality of this annual conference, due primarily to the efforts of the Planning Committee. We also acknowledge the superb efforts of the staff of Conferences and Short Courses for their assistance in organizing the Conference, and Mrs. Linda Bennett for expert sec retarial assistance in the typing of the book. Last, but certain ly not least, we express our appreciation to the various organiza tions that provided the necessary financial assistance. Leonard R. Forte John M. Franz David M. Klachko vii Contents The Receptor Concept: Prejudice, Prediction, and Paradox. . . . . Oscar M. Hechter Discussion. . . . . . . . . . . . . . 41 DeGroot, Hechter, Campbell, Freed, Barnawell, Morgan, Siegel Nuclear Receptors for Thyroid Hormone . 45 Leslie J. DeGroot 69 Discussion ............ ."

This 1987 ORPRC Symposium on Primate Reproductive Biology, the third in a series, marked the twenty-fifth anniversary of the Oregon Regional Primate Research Center (ORPRC). In organizing these symposia, we have emphasized the dedication of many ORPRC staff members to research with nonhuman primates as models for human reproduction. The first symposium in this series, organized by William Montagna, was held in May 1981. Appropriately for a beginning series, its topic was fetal endocrinology. The subject of this year's symposium was the primate ovary, and, as in the past, scientists from around the world, including Sweden, Scotland, England, West Germany, and India met in Beaverton, Oregon, to exchange ideas and information on this important "aspect of reproduction. The international scope of the symposium reflects our belief that both the problems and their solutions extend beyond national boundaries. Many of the nonhuman primates that we rely on as models are endangered as civilization, through population pressure, encroaches on their natural habitats. Without a deeper understanding of how primate reproduction is regulated, and without the control over human population that such an understanding can bring, the quality of life for all primate species may well become substantially diminished. Consequently, we dedicate these symposia to the thesis that a deeper understanding of primate reproductive biology will ultimately improve all primate life. Robert M. Brenner Charles H. Phoenix vii PREFACE Today there is renewed interest in the processes controlling the gametogenic and endocrine functions of the ovary.

Those who are familiar with the two volumes of The Year in Endocrinology may, at first glance, fail to recognize their relationship to the present volume, Contemporary Endocrinology. The name is different and the cover design different, but nonetheless the admonition against judging a book by its cover is very well taken in this instance. In fact, Contemporary Endocrinology is not only the direct linear descendant of The Year in Endocrinology, it is a purposeful clone thereof-the topics are unchanged, the talented group of authors is unchanged, and most importantly, both the objective of the work and the manner in which that objective is approached are unchanged. The objective is, of course, to assist the reader in maintaining currency with respect to important developments, both basic and clinical, in the major areas of endocrinology. We are all much too familiar, unfortunately, with the difficulty of maintaining currency these days. Our approach to dealing with the informational inflation that we are suffering is similar to that used by economists in dealing with monetary inflation, that is, to increase interest. This we have attempted to do by providing for the reader an easy-to-read group of essays in which advances in individual areas of endocrinology are re viewed broadly, synthesized, and placed into perspective by a group of authors who are authorities in their individual fields. They serve, not as guest artists, but as members of a stable Editorial Board that provides continuity by contributing to successive volumes."

Since 1948, the date of publication of Hormones and Behavior by Dr. Frank Beach, this hybrid area has received a great deal of attention from scientists representing various allied fields. As a result, the data and publications dealing with hormones and be havior have increased geometrically and on an annual basis. More recently, a number of review articles and short volumes dealing with aspects of hormones and behavior have been published. How ever, there seemed to be an overwhelming need for a synopsis of the major topics in a unified and integrated form. Thus, the reason for this edition. In these two volumes, we hope we have presented a critical assessment of the various interrelated areas dealing with hormones and behavior. In some instances, we have minimized the presenta tion of certain aspects of psychoendocrinology. This was a con scious effort since some areas have received competent coverage in other volumes. In other instances, we have presented hitherto seldom mentioned material. For example, we are presenting coverage of the general areas dealing with hormones and behavior in aging and the aging process, mental illness, early experience, motivation, genetics and personality. In some instances, the available data is overabundant; in others, the data is scarce. However, we hope that an evaluation of this situation stimulates further interest and further collaborative research where needed.

We had the pleasure and the great opportunity to organize a symposium on "Molecular Biology of Brain and Endocrine Peptidergic Systems" under the auspices of the Canadian Biochemical society and the International Foundation for Biochemical Endocrinology. We were indeed very happy to ass ble a series of first rate speakers who delivered excellent papers on a variety of subjects from the synthesis of complicated peptide analogs, to the creation of trangenic mice, site-directed mutagenesis, enzyme characterization and DNA binding sites. One hundred and seventy-five participants attended the 40 conferences while having the opportunity to look at 24 posters presented by senior scientists as well as students. We, of the organizing committee, feel extremely pleased to have received an overwhelming response from such a group of scholars. We wish to express our sincere gratitude to Mrs. Diane Marcil who arranged most aspects of the meeting with efficiency. We also thank the different organizations and companies for their generous grants which made the reunion possible. We hope that the participants have gained scientifically while having a pleasant sojourn in beautiful Montreal. The organizing committee was made up of a group of dedicated people, particularly its secretary, Dr. Philippe Crine. To all speakers and sessions chairpersons, we are indebted for the excellence of their participation.

The beautiful town of Cavtat near Dubvronic, Yugoslavia was the site of the twelfth meeting of the International Foundation for Biochemical Endocrinology. It was sponsored by the Serbian Academy for Sciences and Arts and by the Foundation. The Croatia Hotel in Cavtat was a splendid place for a meeting. The presentation of the subject matter relating to "Neuroendocrine Correlates of Stress" was interesting and informa tive. The topics included many forms of stress, their mediators and responses. They included: releasing factors; neurotransmitters in the hypothalamus; role of noradrenal ine; the reaction of the hypothalamo-pituitary-adrenocortical axis to stress; immunological stress; thermal stress; immobil ization stress; peptides in shock; stress-induced prolactin; stress and acupuncture; stress and behavior; spinal cord transection and stress; electroconvulsive stress; neuroendocrine cells and stress; protein kinase as a signal transducer; the effects of constant 1 ight and darkness on the pineal; sleep, stress and ovarian function; and finally, hormonal response to exercise. Subsequently, the papers presented were rewritten for inclusion in this monograph. The Chairmen for the sessions at Cavtat were K. McKerns and Stefan Manolov, V. Chong-Li and L. Rakic, S. Feldman and R. Mil in, M. Lee and V. Liposits. The next meeting of the Foundation will be held in Edinburgh near the end of September, 1985. The topic will be "Neuroendocrine Molecular Biology" with Professor George Fink as Honorary Chairman of the local organizing committee."

Although physiological and anatomical evidence had clearly indicated for many years that the secretion of anterior pituitary hormones is under control by the central nervous system, it is only recently that the isolation and determination of structure of three hypo- thalamic hypophysiotropic hormones have been accomplished. This has brought the concept of neurohormonal control of adenohypophyseal function into precise biochemical and chemical terms. The relative ease of synthesis of TRH (thyrotropin-releasing hormone), LH-RH (luteinizing hormone-releasing hormone), somatostatin and their analogues has opened a new era in the field of endocri- nology and has led to a rapid expansion of our knowl- ge of the control of anterior pituitary function. The rapid evolution of fundamental and clinical research on hypothalamic hormones and the many potential clinical applications indicate the importance of inte- grating the knowledge gained in recent years. This is well illustrated in the Proceedings of the International Symposium on Hypothalamus and Endocrine Functions held in Quebec City on September 21-24th, 1975, which indi- cates that impressive progress has been made in large variety of aspects of hypothalamic hormone research.

To obey the precepts of therapeutic rationality, we should avoid treating the "effect" when there is a way to attack the cause. But what is the cause of diabetes? Diabetes is a molecular disease, that is, a disease in which important cellular components are seriously impaired. Eventually, the activities or the products arising from the impairment find expression in various ways, finally culminating in the abnormalities of diabetes. How early is early enough to attempt to delay this sequence of events? What will provide us with the basis to explore ways and means of halting the progression of the pathological process? What are the new approaches for the treatment of early diabetes? The Fourth International Symposium on Early Diabetes, sponsored by the Diabetes Center of the New York Medical College, held in Algarve, Portugal in November 1978, from which this book evolved, attempted to answer some of these questions. A list of the participants, including their affiliations, will be found preceding the index. Rafael A. Camerini-Davalos v Acknowledgments To our sponsors, U.S.V. Pharmaceutical Corp., Pfizer Pharmaceuticals, Ames Company, Hoechst, Frankfurt; supporters, Boehringer, Manheim, Laboratoires Servier, Nordisk Laboratory, The Upjohn Company, Eli Lilly and Company, F. Hoffman La Roche; and contributors, Bayer A. G. Leverkusen, McNeil, Novo Research Institute, ICI Belgium, Hope for Diabetics Foundation, New York, we express our appreciation for the financial support which made possible the Fourth International Symposium on Early Diabetes. THE ORGANIZING COMMITTEE Rafael A. Camerini-Davalos, M.D.

This has been a year of substantial change for The Year in Endocrinology. The first change, though perhaps only a semantic one, nevertheless represents a landmark. Although last year's volume was designated as the first of an annual series, that seemed to me at the time merely a hope-a realistic hope, perhaps, but a hope, nevertheless. With the publication of this year's volume, however, this can accurately be said to be an annual series, one that we trust will fulfill a need and will therefore continue for years to come. Among other changes from last year's volume are some that were originally intended and others that were unintended. In the former category is the substitution of a chapter on water metabolism and vaso pressin, excellently prepared by Dr. Gary L. Robertson, for the chapter on paraendocrine syndromes that appeared last year. Chapters on these two topics will continue to appear on alternate years. Obviously, the non recurring chapter on a topic of special interest has also changed, and this year's comprises a comprehensive review of autoimmune endocrine dis ease by Drs. Jay Silverberg and Robert Volpe. The unexpected change results from the inability of Dr. Louis Avioli to continue as a member of the Editorial Board. Most fortunately, however, we have persuaded Dr. Charles R. Kleeman to join the Board and to be responsible for the chapter on the parathyroid gland and mineral metabolism. Dr. Kleeman has been assisted on the preparation of this chapter by his daughter, Dr."

This book tells the story of diabetes, from ancient times to today, and provides an accessible introduction to the cause, treatment, and impact of the disease.Diseases have a history, and understanding that history helps us understand how best to treat and control disease today. Today's students are confronted with a panoply of often-frightening illnesses and afflictions - the Biographies of Disease series provides necessary information to understand the origin of various maladies, how they impact contemporary society, and how doctors and researchers from around the world are fighting to devise treatments to alleviate or cure these diseases.This volume, Diabetes, covers a disease that has been a common affliction from the beginning of recorded history, but has been increasing in its impact because of changes in diet and exercise, especially among the young. Diabetes examines all aspects of this disease, including: the diagnosis and treatment of diabetes from the ancient period to the present day; the definition of the various types of diabetes, and the role of glucose and insulin; diagnosis and treatment, with an emphasis on prevention for those at risk; the cultural impact of the disease - on individuals, on families, and on the economy; and, the state of current research on new forms of insulin, blood glucose meters, transplants, and weight control.The volume includes a glossary of important terms and a bibliography of accessible works that discuss the disease.

The Center for Population Research of the National Institute of Child Health and Human Development began operations in August 1968 and is engaged in research dealing with health-related popula tion problems. We organize and support projects for the develop ment of new contraceptives and in the broad field of population research in the social sciences o The Center also supports a variety of projects dealing with the mechanism of action and medical effects of contraceptives now in use, particularly oral contraceptives and intrauterine devices. These studies were initiated several years ago at the specific direction of Congresso We were pleased, therefore, with the opportunity to help organize and support this important and timely conference on the "Metabolic Effects of Gonadal Hormones and Contraceptive Steroids," the subject of which forms an integral part of the Center's research program. April, 1969 Philip Ao Corfman Director Center for Population Research National Institute of Child Health and Human Development v PREFACE Progress in science is often associated with either a "sixth sense" or an inevitable timeliness. Both factors, perhaps, led the members of the Endocrinology Study Section of the National Institutes of Health to propose, in 1966, that an expanded view of the effects of gonadal hormones, in general, and the contra ceptive steroids, in particular. was needed. There had been ample evaluations of the clinical symptomatology, contraceptive efficacy, and effects on the reproductive system, but there was a dearth of information on their multiple systemic'metabolic effects."

Perinatal problems in thyroid gland physiology are common but complicated and present a diagnostic dilemma for the primary clinician. In December 1990, an international group of basic and clinical investigators gathered in Longboat Key, Florida to address these issues. The participants included internists, obstetricians, pedia tricians, neurologists, pathologists and basic scientists in cellular metabolism, endocrine physiology, and molecular biology. The presentations contained within this book bring together their most current and vital research related to the field of perinatal thyroidology. This book is based on the dynamic and fruitful exchange of the participants at the symposium. We are indebted to these individuals whose valuable insights and efforts are contained within this text. Barry B. Bercu Dorothy I. Shulman vii CONTENTS Session I Mechanism of Thyroid Hormone Action 1 Leslie J. DeGroot Thyroid System Ontogeny in the Sheep: A Model for Precocial Mammalian Species * . . * * 11 Delbert A. Fisher Pathologic Studies of Fetal Thyroid 27 Development * * * * * * * Douglas R. Shanklin Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, 47 and Behavioral Studies * * * * * * * S. A. Stein, P. M. Adams, D. R. Shanklin, G. A. Mihailoff, and M. B. Palnitkar The Thyroidectomized Pregnant Rat: An Animal Model to Study Fetal Effects of Maternal Hypothyroidism 107 Susan P. Porterfield and Chester E.

The idea for this book developed as an outcome of a multidisciplinary sym posium entitled "Pituitary Adenoma Update" that was held at Tufts-New En gland Medical Center in April 1977. The purpose of that symposium was to put together our current knowledge of the cause of pituitary tumors and discuss the diagnostic evaluation and management that was now appropriate, in light of the rapid advances that had taken place so recently in this area. Those of our colleagues who had presented papers at the symposium, as well as a number of others, were invited to contribute to this volume, which should serve as a presentation of the "state of the art" on all aspects of pitu itary tumors. We felt that such a book would be of value to endocrinologists, neurosurgeons, neuroradiologists, and pathologists who are involved in the investigation or care of patients with pituitary disorders. For a number of reasons, a review of pituitary adenomas seems particu larly timely. Rapid advances have taken place coincidentally in the fields of neurosurgery, neuroendocrinology, neuroradiology, neuropathology, and neuropharmacology. Seven major developments in these areas have occurred independently and almost simultaneously that have virtually revolutionized our approach to pituitary adenomas.

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.

In the summer of 1969, the first Workshop on Control of Renin Secretion was held at Stanford University. At its completion, it was suggested by many of those who attended that a second Workshop be planned in about two years time. Thus the second Workshop on Control of Renin Secretion took place and from this event the chapters in this book had their origin. The setting of this Work shop was the beautiful J & R Double Arch Ranch in Santa Ynez, California which houses the Kroc Foundation. The Foundation, through the kindness of its President, Dr. Robert L. Kroc, provided us with luxurious accommodations, excellent meeting facilities and an atmosphere extremely conducive to the exchange of scientific knowledge, both formally and informally. In addition, the Founda tion assisted financially in the travel expenses of three of our foreign guests and in the preparation of the manuscripts for this book. I know I speak for all of us who attended the Workshop in expressing our sincere gratitude to the Foundation and to Dr. and Mrs. Kroc and their staff. In addition, I personally, as organizer of the meeting and editor, wish to acknowledge the help of many others who made my job much easier. Drs. Davis, Ganong, Luetscher and Tobian kindly took on the jobs of chairing the four sessions and directing the lively discussions which followed each presentation."

This volume is an outgrowth of a symposium held at the University of Michigan, Ann Arbor, Michigan, October 27-29, 1975. This symposium was organized to bring together basic scientists and clinicians for the purpose of exchanging new ideas and the latest information in the area of Steroid Hormone Action and Cancer. The design of the symposium included both formal plenary sessions and informal roundtable discussion groups, the chapters of this volume being drawn primarily from these proceedings. During the last quarter of a century considerable progress has been made toward understanding the molecular mechanisms in volved in steroid hormone action. It now appears that the mechan sim of action of the four major classes of steroid hormones is qualitatively similar. Research during the past decade has demonstrated steroid hormone receptors in a variety of normal and neoplastic tissues. Receptor-containing neoplasms have been shown to be hormone-dependent and undergo regression when treated with hormone antagonists. Natural and synthetic steroids also have been employed for many years to successfully treat various types of cancer, for example: estrogens, androgens and progestagens for breast cancer; estrogens and progestagens for prostatic carcinoma; progestagens for endometrial carcinoma; and corticoids for leu kemias. All of these neoplasms have now been found to possess receptors for the steroids empirically used in their treatment."

As humans ventured into the twentieth century, the industrialized countries were confronted with the scourge of rickets. Although solariums were becoming common in the early 1900s and phototherapy was gaining popularity as a result of the awarding of a Nobel Prize to Finsen in 1903, it wasn't until 1921 when Hess and Unger demonstrated that rickets could be cured by exposure to sunlight that the healthful benefit of sun exposure appreciated. In 1941, Apperly (Cancer Research; 1: 191-195, 1941) noted that the occasional increased risk of skin cancer was associated with a decreased risk of many other more common and serious cancers. The alarming increase in the number of cases of skin cancer, especially melanoma, has caused great concern about the negative role of sunlight in health. The Sixth International Arnold Rikli Symposium on the Biologic Effects of Light was held in Boston, Massachusetts from June 16th - 18th, 2001. The goal of this Symposium was to focus on the very popular practice of tanning either by sunlight or by artificial light sources and the overall impact this practice has on health and disease. The program was organized by members of the Scientific Advisory Committee and my co-chair emeritus, Professor Ernst G. Jung. The Program Committee organized an outstanding state-of-the-art program that was enthusiastically received by the participants.

The human pancreas consists of two organs in one: the exocrine gland made up of pancreatic acinar cells and duct cells that produce digestive enzymes and sodium bicarbonate, respectively; the endocrine gland made up of four islet cells, namely alpha-, beta-, delta- and PP-cells that produce glucagon, insulin, somatostatin and pancreatic polypeptide, respectively. While the physiological role of exocrine p- creas is to secrete digestive enzyme responsible for our normal digestion, absorption and assimilation of nutrients, the endocrine pancreas is to secrete islet peptide h- mones maintaining our glucose homeostasis. The pancreatic functions are nely regulated by neurocrine, endocrine, paracrine and/or intracrine mechanisms. Thus, dysregulation of these pathways should have signi cant impacts on our health and disease. Nevertheless, the underlying mechanisms by which pancreatic functions are regulated remain poorly understood. Recent basic science and clinical studies con rm myriad physiological and pathophysiological roles of the tissue renin-angiotensin systems (RAS). Of parti- lar interest is the recent identi cation of a local and functional RAS in the pancreas, which in uences both its exocrine and endocrine function. Its role in the pat- genesis of pancreatic diseases including diabetes and pancreatitis is increasingly recognized, as is the therapeutic potential of RAS antagonism: RAS blockade l- its disease progression of type 2 diabetes mellitus and impaired glucose tolerance, and may also protect against pancreatic in ammation.

Growth Hormone and the Heart endeavors to bring together knowledge that has been accumulated in the area of GH and the heart, from basic to clinical studies, by research groups working on this topic throughout the world. Lessons from different experimental models and from several human diseases (acromegaly, adult GH deficiency, heart failure) suggest to endocrinologists and cardiologists that GH may not only have a role in the physiology and pathophysiology of heart function, but that GH itself may have a place in the treatment of primary heart diseases (such as dilated cardiomyopathy) or of cardiac complications of hypopituitarism. Growth Hormone and the Heart will be a useful update of the research produced in the field of cardiovascular endocrinology. The Editors also hope that this book will serve as the primary step in the recognition of the wide physiological and clinical significance of GH and heart interactions.

The dramatic recent expansion in genomic information has motivated the development of new approaches to characterize gene expression and function. A critical issue for both basic and clinical endocrinologists is the physiological role of genes involved in regulating endocrine functions. Transgenic technologies allow the translation of genotypic information into specific phenotypes by using gene overexpression or loss of specific gene functions. Murine functional genomics is thus of central importance in modem biomedical endocrine research. Although mice are at present, the preferred mammalian species for genetic manipulations because of the availability of pluripotent embryonic. stem cells and inbred strains and the relatively low breeding and maintenance costs, transgenic rats have also been generated and used to study endocrine physiology. The two basic techniques used in the creation of transgenic animal models are integration of foreign DNA into a fertilized oocyte by random chromosomal insertion and homologous recombination in embryonic stem cells that are then introduced into zygotes. Transgenic mice and rats serve as sophisticted tools to probe protein function, as models of human disease, and as hosts for the testing of gene replacement and other therapies. Embryonic stem cell libraries for mouse gene deletion are being developed, which will make it possible to generate knockout mice rapidly and without the need to analyze gene structure, construct targeting vectors, and screen embryonic stem cell clones. A novel approach to transgenesis for the expression of DNA within adult differentiated neuroendocrine cells in vivo is using viral vectors.

The pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) has attracted the interest of our group during the last three decades. As early as 1969, a Nobel Symposium dealing with this topic was organized in Stockholm. This was followed in 1987 by a Nobel Conference devoted to the same subject. The main purpose of these meetings was to bring together the most distinguished scientists from all over the world and present theories on molecular and genetic mechanisms responsible for the development of glucose intolerance in NIDDM. This idea was followed also in the present symposium, "New Concepts in the Pathogenesis of NIDDM," organized with diabetologists from Toronto in Canada. Our purpose is to biannually organize international meetings covering important aspects of dia betes research, hoping that this type of interaction may result in new concepts and treat ment alternatives. For us, participating in this symposium in September 1992, the meeting in Stockholm was very stimulating and innovative. It is a special pleasure that almost all invited lecturers submitted manuscripts. Thus, the publication of the proceedings of the symposium makes it possible for all interested in diabetes research to share new ideas and findings presented at the meeting. Claes-G6ran Ostenson Suad Efendic Mladen V ranic v CONTENTS REGULATION OF INSULIN SECRETION Impaired Glucose-Induced Insulin Secretion: Studies in Animal Models with Spontaneous NIDDM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C. -G. Ostenson, A. Khan, and S. Efendic Perturbation ofIslet Metabolism and Insulin Release in NIDDM. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 WJ. Malaisse 2 Regulation of Cytoplasmic Free Ca+ in Insulin-Secreting Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

This volume contains the edited proceedings of the Totts Gap Colloquium on Diabetes Mellitus, DILEMMAS IN DIABETES. The Collo- quium, lasting two and a half days, was organized mainly as a dia- logue among experts in the field with different disciplinary back- grounds and, to some extent, differing points of view. The effort was to synthesize existing knowledge, reconciling disparate data and interpretation, and pointing up important areas of ignorance. Thus, the book should serve not only as a summary of recent information on diabetes, but as a reliable guide to the practicing physician as he wades through often conflicting etiologic dogmas and therapeutic practices. The Colloquium was made possible through the generous support of the Geigy Pharmaceutical Company and the conscientious and expert coordination of Mr. Oscar Swarth. The participants were: Dr. George F. Cahill, Boston, Massachusetts Dr. Harvey C. Knowles, Cincinnati, Ohio Dr. Rachmiel Levine, Duarte, California Dr. Lelio Orci, Geneva, Switzerland Dr. Norton Spritz, New York, New York Dr. Roger Unger, Dallas, Texas Dr. Robert Williams, Seattle, Washington Dr. Stewart Wolf, Galveston, Texas Dr. Arnold Lazarow and Dr. I. Arthur Mirsky were to have partici- pated, but unfortunately were ill at the time of the meeting. Others in attendance included five medical students, especially selected from medical schools in the Philadelphia/New York area.

Dr. Robert L. Jackson, Professor of Child Health at the Uni versity of Missouri-Columbia, decided to retire from clinical practice in 1977 and the Department of Child Health planned a con ference in his honor. The Thirteenth Annual MidweSt Conference on Endocrinology and Metabolism also was in the planning stages and scheduled for two days in the fall. It seemed appropriate to com bine the two into an expanded three-day conference. In view of Dr. Jackson's international reputation in the study and care of children with diabetes mellitus, the conference topic was not dif ficult to find. Experts in this field were delighted to be asked to speak at a conference in Dr. Jackson's honor. We selected a number of excellent speakers to survey the physiology and pathophy siology of pancreatic hormones and their effects in diabetes mel litus, to discuss current knowledge of the microvascular complica tions of the disease, and to put it all into the proper historical perspective of where we have been and where we are going. We think the conference achieved its objective to pay meaningful trib ute to a distinguished member of the scientific community. As with any conference, the conversion of the presentations and discussions to the printed page is a long and arduous process. Many manuscripts were completed well after the conference and references often are more recent than the date of the conference."

It is an authentic privilege to have the opportunity to assemble and edit a new volume on "Prolactin," the first in several decades to be devoted to this fascinating hormone in all its aspects. The obvious clinical rationale for understanding prolactin (PRL) is the frequent occurrence of prolactinomas, the most common type of pituitary tumor. Fortunately, medical management of prolactinomas can be based on our under standing of the physiology of hypothalamic control of the lactotroph. Armed with this knowledge, therapies for proiactinomas are highly successful and well tolerated. Be cause of the historical and practical importance of knowledge regarding the hypothala mus-Iactotroph axis, the first chapters of this volume are dedicated to reviewing the physiology, development, and cell biology of lactotroph regulation. Chapters focusing on prolactinomas and related clinical issues follow these. PRL is the primary hormone that is responsible for "parental care" in many verte brate species. This reproductive strategy is not unique to mammals, but it has devel oped through evolution to be the central distinguishing feature of the mammalian life cycle. Among the mammals, mice have become the most effective research species in recent years. This can be traced to the development of a wide range of methods for manipulating mouse genetics, and thereby influencing development, physiology and behavior. Mice also provide a profound illustration of the physiological challenges faced in maternity. Female mice undergo a post-partum estrous, and often are both pregnant and lactating simultaneously.

Since the late 1960s, there has been an acceleration of research focused on understanding how the efferent ducts, the epididymis, and the vas deferens function with respect to the maturation and storage of spermatozoa and as hormone dependent tissues. Another major interest in the epididymis is that it is an attractive target for the development of male contraceptives. There are well over 16,000 peer reviewed articles in the literature on these tissues, their structure, gene expression, protein synthesis and function. Regular international meetings have been initiated that are dedicated to this field. Thus, there is an urgent need for a comprehensive reference volume that spans every facet of epididymal biology, from historical background to the most current results, from basic cell and molecular biology to clinical issues. Well-established experts from every part of the world have contributed to this volume. By necessity, each author was given page limitations so that many topics are not dealt with exhaustively. Whenever possible, references to more comprehensive discussion of specific topics are included.