Publication of this monograph acknowledges great strides made in research on the zona pellucida during the past decade or so. The body of work presented testifies to a resurgence of interest in the zona pellucida, prompted largely by a renewed appreciation of its unique properties and its important functions during early mam malian development. It is gratifying to realize that the zona pellucida has at last achieved a well-deserved attention. Whereas extracellular coats of nonmammalian eggs have been studied intensively for many years, the zona pellucida by comparison, has until now taken a back seat. Fortunately, the research presented here signals an end to this situ ation. Many of the difficulties inherent in working with relatively small amounts of material have been overcome, paving the way for application of a wider variety of experimental approaches to the zona pellucida by a larger community of investigators. Hopefully, this monograph will serve as a catalyst in this regard. As revealed in these pages, application of contemporary experi mental methodologies has had significant impact on both pure and applied research on the zona pellucida. For example, modem im munological approaches have been used to assess molecular fea tures of zona pellucida structure and function, as well as to evalu ate the zona pellucida as a potential contraceptive target antigen."

It is well established that progesterone plays a role in the brain and hypophysis as a facilitator and inhibitor of sexual behavior and gonadotropin release in the female rat (Everett 1961; Caligaris et al. 1971; Brown-Grant and Naftolin 1972; Dorner 1972; Meyerson 1972; Barraclough 1973; Goldman and Zarrow 1973; Mann and Barraclough 1973; Freeman et al. 1976; Feder and Marrone 1977; Goodman 1978; Attardi 1981), guinea pig (Morin and Feder 1974), and primates (Odell and Swerdloff 1968; Spies and Niswender 1972; Yamaji et al. 1972; Karsch et al. 1973; Dierschke et al. 1973; Knobi11974; Clifton et al. 1975). In an attempt to learn whether a specific progesterone uptake mechanism exists in the brain and the hypophysis, the distribution and retention pattern of radioactivity after in vivo injection of labeled progesterone was studied. Early work of Kato (1963) did not show a selective uptake of radioactivity in the hypo- thalamus of immature and estrogen-primed immature rats after injection oflow- specific-activity [14C]progesterone, but some tendency of the reticular formation to take up radiation was observed. Laumas and Farooq (1966) reported that after intravenous administration of labeled progesterone to ovariectomized estrogen- treated rats, radioactivity in the brain and pituitary appeared to show a very slight, insignificant increase 1-2 min after injection, but the uptake pattern was not definite, as had been seen with estradiol. Seiki et al.

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.

The secretion of bioactive products by tumors of the gastroenteropancreatic system results in the development of watery diarrhea that can lead to death in a very short period if not brought under control. Even if the consequences are less dramatic, the patients' ability to lead a normal daily life is seriously impaired, and they may become severely depressed. SandostatinR alleviates the condition by inhibiting peptide release, and its long duration of action makes it an effective and rational adjunct to therapy at all stages. Last year a consensus Round Table Meeting was held in Scottsdale, Arizona, to discuss the optimal use of SandostatinR in this indication. These guidelines offer the results of clinical research and the dosage recommendations arising from them, together with a critical summary of the points of view presented.

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."

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."

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.

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."

In the middle of the 17th century, the great French philosopher Rene Descartes wrote (L'Homme, J. Le Gras, Paris, 1669) that a suitable stimulation of the brain results in two types of "movements": exterior movements, designed to seek desirable ends and to avoid undesirable or harmful ones and interior movements or "passions" which through the release of "animal spirits" regulate the heart, the liver, and other organs. When it appears appropriate to meet a threat with force, the passion of rage causes the release of strong spirits, whereas when avoidance appears to be the better choice, the passion of fear causes the brain to release weak spirits. We do not know what influence, if any, Descartes had on the thinking of Walter B. Cannon (Bodily Changes in Pain, Hunger, Fear and Rage, Appleton and Co. , New York, 1920), of Hans Selye (The Story of the Adaptation Syndrome, Acta, Inc. , Montreal, 1952), ofG. W. Harris or of R. Guillemin (Hypothalamic-Hypophysial Interrelationships. A Sym posium. c. c. Thomas, Springfield, 1956), but it is interesting to reflect upon the durable value of great ideas which constantly resurface even if modified by other ideas and by new techniques, as if propelled by a preordained intellectual imperative.

"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."

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 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."

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."

more intuitive study to greater empiricism. Frequently, chapters are di vided into discrete sections to discuss each rather distinct era of inquiry. This approach, when used, can provide a valuable historical overview of the early clinical formulations about each disease. Even though many of the earlier research philosophies and techniques may seem so simplistic as to mitigate against their inclusion, early research hypotheses were often generated from astute observation of clinical findings and relationships. In addition to shaping later empirical questions, a review of historical ante cedents provides a yardstick by which to measure the progress of more current studies, even though much is yet to be learned. As is true of any refinement of knowledge, the juxtaposition of the two approaches of study reveals that some of the early postulations about patient attributes and disease consequences have been confirmed, while other suppositions have been discarded. Although the generally subjective assessment methods used in the early studies may not have provided an optimal data base, it is interesting to note which clinical impressions were able to withstand greater empirical rigor and which were not. The book at its inception was intended to provide a succinct introduc tion to psychoneuroendocrinology research for practitioners and scientists who might be relatively unfamiliar with the area. However, it quickly became apparent that the sophistication of the information could not be readily reduced without vast oversimplification and loss of substance."

For many years now, our understanding of the somatotrophic and reproduc tive axes has evolved essentially independently, both fields of study reaching a highly advanced, although far from complete, level of under standing. Along the way, however, it became apparent that in some circumstances the reproductive and somatotrophic axes may be inter dependent. Inklings to this effect were at times feeble and at other times more convincing. Among those inklings are the clinical recognition by pediatric endocrinologists of the apparent association between isolated GH deficiency and delayed puberty, as well as of the apparent permissive, pUberty-promoting property of GH. Equally important is a body of experi mental studies establishing the ovary of multiple species as a site of GH reception and action. Arguing against an essential role for GH in the reproductive process is the observation that individuals who have GH resistance of the Laron variety are fertile arid that isolated GH deficiency does not constitute an absolute barrier to the attainment of sexual maturation and fertility. The intraovarian insulin-like growth factor (IGF) hypothesis proposes that IGFs may serve as amplifiers of gonadotropin action. Although the dependence of intraovarian IGFs on systemic GH action has never been unequivocally demonstrated, that leap of faith has often been made. The intraovarian IGF hypothesis serves as the rationale for the adjunctive use of GH in the induction of ovulation."

The fact that certain adrenal steroid hormones are immunosuppressive and anti-inflammatory has been known for many years, and is routinely exploited by physicians. These effects are attributable to glucocorticoid steroids such as cortisol. Pharmacological doses of glucocorticoids inhibit most or all T cell types. However we now know that the effect of exposure to raised physiological levels is mainly to drive developing lymphocyte responses towards a Th2 cytokine profile (interleukin-4 secreting) while suppressing the development ofThi (gamma interferon- secreting) lymphocytes. Only recently have two further regulatory mechanisms become appar- ent. First, these effects of cortisol are balanced by pro-inflammatory and ThI-enhancing effects of another adrenal steroid, dehydroepiandro- sterone sulfate (DHEAS). Second, the activity of cortisol is directly modulated by enzymes in the target organs and lymphoid tissues that convert it into inactive cortisone. This new information leads to the possibility that immunoregulatory steroids could be used by physicians in novel ways. We can envisage steroid combinations that exploit the anti-inflammatory effects of corti- sol, while the Thi-suppressing and Th2-promoting properties of these hormones are opposed by derivatives of DHEAS. Such therapies are already proving effective in animal models of infection, and could revol- utionize treatment of Th2-mediated diseases such as asthma, where the anti-inflammatory effects of cortisol are desirable but the effects on T lymphocyte differentiation are not.

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.

A little over 12 years ago I wrote a small volume entitled Infertility. It seemed to me at that time that significant advances in the field called for the publication of such a volume. The following is from the preface to that volume: During the past 15 years considerable progress has been made in the field of infertility diagnosis and management. It is perhaps a paradox that much of this increased knowledge has come about because of Western medicine's preoccupation with the search for a means to control reproduction. As a result, we have achieved new insights into the physiologic mechanisms involved in reproduction, and we have found better methods for measuring physiologic changes in reproductive health and disease. To these advances can be added improvements in the utilization of endoscopic and surgical techniques, in the diagnosis and treatment of infections and endometriosis, and in the treatment of hormonal disorders. During this period, too, through workshops and conferences and in journals and texts, these latest advances have been made available to physi cians, an outstanding example being the two volumes of Progress in Infer tility, edited by Drs. Jan Behrman and Robert Kistner. As necessary as these publications are, they do not offer an overall view of infertility diag nosis and management."

The importance of osteoporosis in the United Kingdom as a cause of death and disability is now well recognised. There are in excess of 200,000 osteoporotic-related fractures in the UK per annum asso ciated with an estimated cost of GBP942,000,000. Following hip fracture it is known that about 50% of patients are unable to live indepen dently and about 20% of such patients die within the first 6 months. These figures, compelling as they are, reflect poorly on current medical practices which manifestly have failed to identify patients with low bone density at risk of fracture. The hope is that the techni cal advances which have enabled bone mineral density, and other allied indices, to be measured with high precision and accuracy offers the chance of identifying patients at risk of fracture and guiding the clinician to make treatment decisions which may reduce the patients' risk of fracture. In the UK, services for identifying patients at risk of fracture are still in their infancy and are not uniformly available throughout the country. This situation is, however, likely to improve particularly fol lowing the publication of the Royal College of Physicians report "Osteoporosis -clinical guidelines for prevention and treatment" and the recognition in "Our Healthier Nation" that osteoporosis pre vention should be included as a target to achieve a reduction of 20% in accidents by 2010.

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.

This volume in the series Developments in Medical Virology deals with viruses involved in diabetes mellitus, a syndrome with a strong genetic background that causes damage to the regulation of insulin synthesis and function. Viruses were found either to cause or to stimulate diabetes mellitus in man and in animal models. The nature of the role of viruses is described by many of the scientists who participated in the original studies. To complete the picture, chapters were included that deal with the insulin gene, the secondary structure of the proinsulin and insulin receptor polypeptides, pancreatic Langerhans islets, and clinical considerations of the disease. The aim of Developments in Medical Virology is to elucidate processes involving viruses as pathogens of cells and organisms, with special attention to human diseases. A number of volumes will be devoted to viruses affecting specific organs (e.g. brain, liver, etc.), while others will elaborate on the clinical experience in the use of antiviral drugs. The series is published in parallel with Developments in Molecular Virology, designed to present an analysis of molecular mechanisms implicated in virus infection and replicative processes. In addition, the series Developments in Veterinary Virology provides information on viruses causing diseases in animals, with special emphasis on aspects of interest to veterinarians.

During the last decade, circadian and episodic fluctuations of the plasma levels of pituitary hormones have been demon~ trated in man. The interest in the time dependence of the pituitary secretions partially originates from their close functional relation with the neuroendocrine mechanisms pre- sumably responsible for the control of the circadian.rhyth- micity in man. High frequency blood sampling techniques and specific radio- immunoassays have allowed to describe in detail the varia- tions over the 24-h cycle of the hormonal concentrations in healthy individuals under basal conditions as well as after manipulation of external synchronizers such as the sleep- wake cycle, the dark-light cycle and the feeding schedule. Alterations in normal hormonal var~ions have been sugges- ted to play a role in the etiopathogeny of several metabo- lic and mental diseases, such as obesity or manic-depressio~ Important clinical implications regarding treatment and pre- vention are expected to be developed in the near future. However, so far, data obtained in different groups are dif- ficult to compare because different hormones were studied using different protocols and statistical methods. As a result, unclear or controversial issues are not uncommon.