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.

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

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

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

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

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."

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

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

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

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.

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."

Carole Mendelson has assembled a panel of leading investigators to critically review the various classes of endocrine, paracrine, and neuroendocrine factors that play a role in the regulation of lung development and surfactant production. Special attention is accorded the actions of glucocorticoids in lung development and the synthesis of surfactant glycerophospholipids and proteins. Also extensively treated are the roles of cell-cell interactions and the elaboration of various growth factors and bioactive peptides in pulmonary cell differentiation, gene expression, and pathophysiology. State-of-the-art and comprehensive, Endocrinology of the Lung constitutes a powerful new standard guide that illuminates the complex endocrinology of the lung for all those actively investigating hormone action in pulmonary biology and medicine today.

Calcium plays an enormous and varied role in living systems now widely appreciated by clinicians.
Calcium in Internal Medicine demonstrates the physiological significance of calcium in clinical medicine and discusses the abnormal calcium metabolism in disorders such as renal failure, hypertension, atherosclerosis and osteoporosis.
Hirotoshi Morii (Editor) linked the clinical use of vitamin D analogues in bone diseases, Yoshiki Nishizawa (Editor) researched the connection between calcium metabolism and atherosclerosis and Shaul G. Massry (Editor) was the first to systematize the importance of excess PTH in chronic renal failure. In addition to these areas, Calcium in Internal Medicine covers basic physiology, pathophysiology, nutritional requirements and the role of calcium in the development and treatment of other various diseases. The importance of calcium and its regulatory systems is brought together in one publication providing a useful reference tool for internists, rheumatologists and endocrinologists.

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.

Relaxin, perhaps more than any other hormone, has a varied history of eliciting enthusiasm, rejection, skepticism, and long lapses of neglect. Long after its discovery, it was a hormone in search of a physiological role in humans. Today, relaxin is implicated in mammary growth, development and function, ionotropic and chronotropic action on the heart, and angiogenic activity in both the peripheral tissues and the endometrium. It is best known for its effect on the uterus and the symphysis pubis in preparation for parturition. However, the literature suggests that not all functions occur in one species. This book describes how to obtain the necessary molecules or derivatives for research, reaching right into the design of new molecules for specific applications.

The flow of information in neuroendocrinology and related disciplines is vigorous, favored by the availability of sensitive and specific biochemical and histochemical techniques that advance our knowledge of CNS neurotransmitter and neuropeptide systems. Volume 8 of Neuroendocrine Perspectives illuminates new findings inthis areawhich add complexity to the traditional view ofthe hypothalamo- pituitary control, and to established concepts ofthe modulation ofbrain function by target hormones. In the first chapter, Ben-Jonathan exhaustively reviews evidence derived from her own work that demonstrates the importance of the posterior lobe as a regulator of prolactin secretion via two opposing influences, i. e. , dopamine released by the tuberohypophyseal dopaminergic system into the short portal vessels and a prolactin-releasing factor which is produced locally, though the identity of its innervating neurons is still unclear. Despite the wealth of information on prolactin and its cell of origin, little is known about the manner in which the hormone exerts its effects on target cells. Frawley and coworkers thoroughlyexamine the direct actions ofprolactin on a broad spectrum ofmammalian tissues, dealing extensivelywith prolactin receptors and the putative second messengers. They also review new evidence, based on their original findings, for an indirect action ofprolactin exerted through the livervia synlactin and liver lactogenic factor, two extracellular modulators ofthe biological functions ofthe hormone. The relationships among the CNS, neuroendocrine and immune systems are bidirectional and constitute an integrated loop.

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."

Lipids and Women's Health is an up-to-date critical review of pertinent scientific and clinical issues connected with lipid disorders in women. Topics discussed include the public health significance of cardiovascular disease in women, lipoprotein and lipid metabolism, effects of estrogens and progestins on lipid metabolism, metabolic changes of menopause, and the paradox of obesity, a curable disease that is rarely cured, as well as those conceptual advances in our understanding of diabetes mellitus that have clarified diagnosis and may have improved treatment. The relationship of diet and lipid intake to the development of breast and uterine cancer; dietary and drug treatment of lipid disorders; effects of exercise, smoking, and stress; and repercussions of lipid disorders on the family are explored. The volume should prove of use to gynecologists, internists, family practitioners, and pediatricians, as well as to all other professionals with a major concern for the health of female patients.

A central concept in the evolutionary theory of senescence is the idea that ageing results from life-history trade-offs. In particular, the disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. Comparative studies among mammalian species confirm that cells from long-lived species appear to have a greater intrinsic capacity to withstand stresses than cells from short-lived species. Childbearing at older ages has become increasingly common in modern societies because of demographic changes, medical progress and personal choice. While the detrimental effects of late reproduction on infant mortality and genetic diseases have been well documented, little is known about the possible postponed detrimental effects of late parenting.

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita tive change in GH secretion was the net result of pituitary stimulation and inhibition by the hypothalamic neurohormones, GH releasing hormone (GHRH), and somatostatin (somatotropin release inhibiting factor; SRIF), respectively. During the 1970s, another endocrine research pioneer, Dr. Cyril Bowers, discovered that structural modification of enkephalin re sulted in a family of peptides with GH releasing properties. These com pounds, simply called GH releasing peptide (GHRP), were originally thought to mimic GHRH. However, upon subsequent investigation they were found to supplement the activity of the natural hormone through a different mechanism. Nearly two decades after their discovery, the differ ences between GHRP and GHRH have been described by many different laboratories throughout the world. The complementary GH secretagogues have different binding sites, second messengers, and effects on gene expres sion. Based on these differences, it has been suggested that expansion of the original two hormone mechanisms for GH regulation to include a third molecule may be appropriate, even though the naturally occurring ana logue of GHRP has not yet been identified. Despite our lack of knowledge concerning the natural product mimicked by GHRP, clinical development of the new family of GH secretagogues for diagnostic and therapeutic purposes has begun in earnest."

"Fertility Preservation in Males: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this practical reference guide provides an update on options for fertility preservation in men, while also discussing important related epidemiologic, ethical, medico-legal, psychological, and social aspects. Using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms, the chapters all conform to a uniform structure, including step by step protocol of laboratory procedures, key issues in commentary and a list of references. The result is a unique resource for reproductive endocrinologists, urologists, embryologists, reproductive scientists, and oncologists."

A growing majority of women in the western hemisphere have been delaying initiation of childbearing to later in life. Consequently, more than ever before, women in their late 30s to early 40s are attempting their first pregnancy. Since the incidence of most cancers increases with age, delayed childbearing results in more female cancer survivors interested in fertility preservation." Fertility Preservation in Females: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this unique and practical reference guide for reproductive endocrinologists, gynecologists, embryologists, reproductive scientists, and oncologists provides strategies for fertility preservation in women, using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms."

Cell biology has made an appreciable impact on the evaluation of physiological and pathophysiological processes leading to a more detailed understanding of the signaling mechanisms by which cells communicate in vivo and in vitro and modify adaptively. By using cell culture models in addition to animal experiments we are now able to better define the overall and the selective potential of drugs. This book is designed to give information on the advantages and limitations and on new aspects and the meaning of cell culture models in pharmaceutical research.

The islets of Langerhans, the primary source of hormone production in the pancreas, have been the focus of research into the nature of diabetes for decades. In recent years, the molecular biology of this multiendocrine organ has been intensively investigated, with a corresponding increase in our understanding of the normal and pathological functioning of islet cells. Molecular Biology of the Islets of Langerhans provides a comprehensive treatment of molecular studies on the synthesis of insulin, glucagon, somatostatin and pancreatic polypeptide. In addition, this volume presents contemporary hypotheses and explanations, at the molecular level, of the defects in islet cells that may lead to diabetes. The material presented here will be essential reading for researchers in human endocrinology and, in particular, for those working in the area of diabetes research.