For out of olde hokes, in good feyth, Cometh all this newe science that men lere. Geoffrey Chaucer The Parliament of Fowls During the past two decades knowledge of the human menstrual cycle and of normal and abnormal reproduc- tive function has increased at a dramatic rate. As rec- ognized in this volume, this explosion of knowledge is due in large measure to the development of radio- immunoassays for the measurement of the minute quantities of reproductive hormones found in the cir- culation. Yet the foundations for the many recent developments were laid well in advance. The concepts and hypotheses tested were often suggested even be- fore the hormones involved were identified and iso- lated. A consideration of the historic aspects of re- search in this field places recent research in the appropriate perspective. Moreover, as presented by Drs. vii viii FOREWORD Gruhn and Kazer, the history of progress in this field makes fascinating reading. A review of the history of reproductive endocri- nology should be required reading for all students of the subject and reproductive endocrinologists in train- ing. Dr. Griff T. Ross, a noted reproductive endocri- nologist, often instructed his students that every hy- pothesis he tested could be found in some form in the publications of previous scientists. The answers to present and future questions are often hidden in the lessons of the past.

This volume presents the proceedings of a symposium on the "Control of the thyroid gland~ regulation of its normal function and growth," held at the National Insti- tutes of Health, Bethesda, Maryland on March 20 and 21, 1989. Our motivation for the organization of this symposium was the fast development in re cent years of our understan- ding of the regulation of the thyroid - and the progress in the field of cell regulation in general - which have led to profound modifications of our view of the control of the thyroid. Not so many years aga the thyroid was thought to be controlled by one regulator, the pituitary TSH, which with cyclic AMP in the role of second messen- ger was considered to express or regulate most or all processes in the gland. In the last several years it has been weIl documented that hormones other than TSH and various growth factors are involved in thyroid growth con- trol and it has been increasingly clear that several hor- mones and neurogenic agents are obligate participants in the regulation of thyroid function. In addition, not only new agonists acting on the thyroid have been revealed, but new transducer and second messenger systems have been discovered. In particular the interest has been - and is- focused on the signals emanating from the hydrolysis of the inositol phospholipids, comprising the inositol tris- phosphate/Ca2~ pathway and the diacylglycerol/protein kinase C pathway.

Almost every aspect of energy and nutrient metabolism is altered by hormonal and other physiological changes during pregnancy and lactation. While it is evident that hormonal adjustments affect nutrient requirements, these are rarely considered when nutrient recommen dations are made for pregnant or lactating women, and often neglected during evaluation of nutritional status. In addition, changes in nutrient metabolism during the stages of pregnancy and oflactation are usually considered separately, while in reality events during pregnancy can have a major influence on nutritional status and nutrient requirements during lactation. The purpose of this volume is to describe changes in the metabolism of important nutrients during pregnancy and lactation, including the physiological basis for these changes and their implications for nutrient requirements and assessment. Authors have considered such issues as inter-relationships between endocrine changes and nutrient metabolism at the tissue, cellular and molecular level; alterations in nutrient binding proteins; the efficiency of nutrient absorp tion and retention; and the impact on maternal as well as fetal nutritional status. Another unique aspect of this book is the focus on pregnancy and lactation as a continuum."

THIS BOOK collects together papers given at a NATO Advanced Research Workshop held at Il Ciocco (Lucca), Italy, from the 9th to the 15th April, 1989. It sets out to present the current state of understanding of the principles governing the way fluxes and concentrations are maintained and controlled in metabolic systems. Although this is a topic that has held the interest of biochemists for many years, it is only quite recently that the methods of analysing the kinetics of multi-enzyme pathways developed over the past two decades have come to be widely discussed or applied experimentally. Many biochemists remain sceptical that the new methods offer a real advance (except in complexity) over the landmark discoveries of the 1950s and 1960s relating to inhibition of enzymes at branch-points by the end products of metabolic pathways, and the interpretation of allosteric effects and cooperativity. Even those who have become convinced that the classical ideas provide only the starting point for understanding metabolic control have been by no means unanimous in their assess ment of the direction in which one should advance. In this book we have tried to include all of the current points of view, including the view that the classical theories tell us all that we need to know. We have not seen it as our role as editors to paper over the cracks that exist and to pretend that we can speak to the world with one voice."

Recent progress in recombinant DNA technology and the availability of a number of nonpeptide subtype-specific receptor antagonists and of specific antibodies to components of prorenin-renin-angiotensin system (PRAS) have led to rapid advances in the under standing of the multifaceted role of angiotensin II, classically known as a peptide hormone of cardiovascular homeostasis. Accumulating evidence sug responsible for the regulation gests that, in addition to its role in salt and water metabolism, PRAS may control other physiological functions including neurosecretion, cellular proliferation, hypertrophy and/or differentiation, angiogenesis and gonadal function. At the same time, it is becoming evident that the specialized functions of endocrine glands are not only regulated by trophic hormones but also by locally produced paracrine/autocrine factors. The concept is emerging that tissue PRAS is one such locally active regulatory system. With more and more reproductive and endocrine organs being added to the list of tissues that contain a local tissue PRAS, questions are being raised by the reproductive biologists and endocrinologists as to the role of such systems in the tissues of their interest. On the other hand, the cardiovascular and renovascular physiologists are wondering about the relevance of PRAS in various peripheral tissues compared to those of the classical cardiovascular organs. It appeared, therefore, that the time was ripe for a meeting to consider a merger of interest in these two important but heretofore distinct areas of physiology."

Originally presented as the author's thesis (doctoral--Technical University of Denmark).

The use of cells for the treatment of a variety of diseases is no longer a dream. Today, blood transfusion, bone marrow transplantation, the use of ex vivo cultured skin in wound healing, and peripheral stern cell transplantation, including the ex vivo expansion of hematopoietic stern cells after high-dose chemo/radiation therapy, are routine. This high standard of knowledge and skills in cell transplantation might also re sult in tackling hitherto untreatable diseases. Organ transplantation is presently the only life-saving treatment for a variety of conditions. Important findings in cell and molecular biol ogy, the identification of hematopoietic, mesenchymal and neuronal stern cells, together with breakthroughs in the methodology for isolat ing, purifying, expanding, and storing human cells could make cellular therapy an alternative to organ transplantation in certain diseases within the next decade. Placental blood may be the source of choice in isolating naive progenitor cells for allogeneic transplantation. Immunotherapy is the most hopeful strategy to date for the treat ment of tumors resistant to chemotherapy, radiation therapy, or hor mone therapy. It includes the use of tumor-infiltrating lymphocytes, ex vivo activated memory T lymphocytes, and cell-based vaccines."

The disorders induced by iodine deficiency affect at least one billion people. Because ofits effects on brain development, iodinedeficiency is the single most preventable cause of mental retardation in the world. Therefore, the United Nations and the Heads of State of almost all the world's countries represented at the Summit for Children in 1990 adopted resolutions to eradicate the disorders induced by iodine deficiency (IDD) by the year 2000. For geological and socio-economic reasons, most of the populations affected by iodine deficiency disorders live in isolated and usually mountainous areas, in pre industrialized parts ofthe world. The problem of iodine deficiency in Europe has been greatly underestimated in the last decades. After the remarkable studies on the effects of iodine deficiency and their prevention and correction in Switzerland, IDD was generally considered no longer a significant public health problem in Europe. However, surveys carried out in the early 1980's under the auspices of the European Thyroid Association, clearly demonstrated the persistence of moderately or even severely affected areas. These surveys also highlighted the lack ofinformation about large parts ofEurope, especially its eastern part. It is only quite recently, following major changes in international relations and thanks to the support of UNICEF, WHO, the International Council for the Control of Iodine Deficiency Disorders and the European Thyroid Association, that more extensive surveys have been conducted in several parts of Europe hitherto almost unexplored. These surveys showed that most European countries were iodine deficient."

It has been ten years since the National Hormone and Pituitary Program (then called the National Pituitary Agency) sponsored a symposium on human growth hormone (hGH). Numerous advances have occurred during this period. This book does not attempt to summarize past achievements. Rather, it deals with the contemporary issues in hGH research. A discussion of the present state of the art, of necessity, includes a review of the past. Some of the topics herein discussed include the following: 1. Growth hormone releasing factor (GRF). In 1973, the growth hormone inhibitory factor (somatostatin) had recently been discovered. The search for a releasing factor in humans led to its discovery not in the pituitary but in a pancreatic tumor that secreted growth hormone. The advances are discussed in this book. The current hope is that GRF will eventually become an effective therapeutic agent for idiopathic hypopituitarism in childhood and adolescence. 2. Biosynthesis of hGR by recombinant DNA technology. Current advances are discussed. Although hGH is not yet an approved drug, it will eventually become one. This will broaden our horizons in terms of hGH effectiveness in disorders other than hypopituitary dwarfism. The current experience with this type of hGH in both the Vnited States and Europe is reviewed by several authors.

Diabetic nephropathy is a tragic illness. Its often insidious onset in the insulin dependent (type I) diabetic, typically a young adult, heralds the last act in the course of a disease that will increasingly become the dominant preoccupation in the patient's shortened life. For most type II diabetics, the beginning of clinical renal insufficiency is but a phase in a continuous deterioration that affects the integrity ofjob, marriage, and family. The nephropathic diabetic is hypertensive, has worsening retinopathy, and more often than not, is also plagued by peripheral vascular insufficiency, heart disease, gastrointestinal malfunction, and deepening depression. Until the 1980's, few type I diabetics who became uremic (because ofdiabetic nephropathy) lived for more than two years. Hardly any attained true rehabilitation. This dismal prognosis is changing substantially for the better. Research in diabetes has resulted in striking advances at both ends of the type I diabetic's natural history. In one exciting clinical trial now underway in London, Ontario, halfofchildhood diabetics treated with cyclosporine within six weeks of onset evince"permanent" disappearanceofhyperglycemia and the need for insulin. At the otherendofthe natural historyofdiabetes for the nephropathic patientwith worsening eye disease (renal-retinal syndrome), who receives a kidney transplant, patient and graft survival, two years after cadaveric kidney transplantation in type I diabetics is now equal to that of the nondiabetic."

Stuart Handwerger, MD and a distinguished panel of clinicians and experts review the most significant recent developments in molecular and cellular biology, powerful advances that have produced new diagnostic methods and improved treatments for many pediatric endocrine diseases. Topics range from the growth hormone/prolactin/placental lactogen gene family and their regulation of growth, to steroid hormones, sexual development, and mineral corticoid action. Additional chapters examine the pathophysiology of insulin-dependent diabetes mellitus, the molecular genetics of thyroid cancer, the molecular basis of hypophosphatemic rickets, and inherited diabetes insipidus. Molecular and Cellular Pediatric Endocrinology offers today's clinicians and researchers not only the latest findings on endocrine diseases in their pediatric manifestations, but also highly practical insights into today's cutting-edge diagnostics, treatment strategies, and powerful new therapeutics.

Male Reproductive Function gives an up-to-date review on the physiology and disease processes associated with the male reproductive system. The first few chapters describe the regulation of the functions of the testis and the integration of its components: germ cells, Sertoli cells and Leydig cells. This is followed by a description of puberty and aging, and the disorders or dysfunction that may be associated with these physiological processes. Discussions on the current methods for the diagnosis and treatment of male hypogonadism, male infertility and male sexual dysfunction follow, with detailed descriptions of types of androgen replacement and the benefits and risks of such treatment. The book concludes with the development of male contraception and the possible influence of the environment on the male reproductive system. Male Reproductive Function represents a conglomeration of the efforts of experts in andrology from all over the world, both in basic cellular/molecular biology as well as in clinical science and practice. This book is suitable for endocrinologists, urologists, general internists, gynecologists and other students in the field of male reproduction.

Proceedings of the First International Meeting of the Pancreatic Islet Study Group held in the Alicante, Spain, November 25-28 1994

The prevalence of hypertension is almost three times as high as that of diabetes mellitus type 2, with both conditions being major risk factors for stroke, ischemic heart disease, cardiac arrhythmias, and heart failure. The exact prevalence of hypertension related to hormonal derangements (endocrine hypertension) is not known but estimated to affect less than 15% of hypertensive patients. Recent scientific discoveries have increased the understanding of the pathophysiologic mechanisms of hypertension. In Endocrine Hypertension, a renowned panel of experts provides a comprehensive, state-of-the-art overview of this disorder, discussing when to assign an endocrine cause in one of many conditions that may present with hypertension. The first part of Endocrine Hypertension is dedicated to adrenal causes. The second part of the volume concerns potential nonadrenal causes of hypertension, such as growth hormone excess or deficiency, primary hyperparathyroidism, vitamin D deficiency, testosterone deficiency, insulin resistance, obesity-associated hypertension, and the role of central mineralocorticoid receptors and cardiovascular disease. An important contribution to the literature, Endocrine Hypertension is an indispensable reference not only for endocrinologists, diabetologists, and adrenal investigators, but also for translational scientists and clinicians from cardiology, internal medicine, pediatrics, family medicine, geriatrics, urology, and reproductive medicine / gynecology.

A 1981 treatment of the action and uses of the hormones and drugs that influence endocrine functions in the body as seen by a pharmacologist. The book includes a description of available drug preparations and expected therapeutic responses, and an examination of their side effects and interactions with other drugs. Special emphasis is placed on how such drugs and hormones work and on how their biological effects are related to their chemical structures. The physiological background to the practical significance of such substances is given for both a healthy and a diseased state. The book assumes little prior knowledge of endocrinology or pharmacology.

Proceedings of the Third Hans Selye Symposium on Neuroendocrinology and Stress held in Budapest, Hungary, August 17-21, 1992.

The discovery of hypothalamic factors that inhibited growth hormone secretion and of pancreatic factors that inhibited insulin secretion were the first clues to the existence of somatostatin. During the course of efforts to isolate growth hormone releasing factor, Krulich, McCann and Dhariwal found that hypothalamic extracts contained a potent inhibitor of growth hormone secretion. They postulated that growth hormone secretion was under a dual control system, one inhibitory and the other excitatory (I) . In studies being carried out at about the same time, Hellman and Lernmark found a factor in pancreatic extracts that inhibited insulin secretion (2). They postulated that islet cell function was regulated by local hormonal factors. With the isolation and chemical characterization of somatostatin by Brazeau and colleagues (3), and the availability of relatively large amounts of the synthetic peptide for research, it has been possible to demonstrate that both predictions were true. Subsequent work revealed that somatostatin, as initially isolated (somatostatin 14), was but one of several related peptides, part of a multigene family, with tissue specific processing. Many of the details of biosynthesis and genetic control have been worked out, and this molecule has served many workers as a model gut-brain peptide for detailed study. The peptides are widely distributed in tissues and exert an extraordinary range of effects on most glandular secretions, both internal and external.

Most of the following chapters were presented as plenary lectures or symposium talks at the 1986 XXXth Congress of the International Union of Physiological Sciences in Vancouver, B.C. A distinguished international group of endocrinologists and physiologists have contributed up-to-date reviews of their particular fields. The early chapters are largely concerned with the brain and neuroendocrine mechanisms controlling the secretion of gonadotropin releasing hormone (GnRH) and its action on the anterior pitui- tary gland. Later chapters focus on the gonads themselves and the systemic and intrinsic hormones influencing the functional cytology of ovarian and testicular cells. Such comprehensive subjects as sex differentiation, puberty, placentation and parturition are also discussed authoritatively. According to Pfaff and Cohen and Arai et al., gonadal steroids, especially estrogen, exert multiple effects on certain hypothalamic and preoptic neurons, including growth, protein synthesis and electrical changes, which promote plasticity and facilitate synaptogenesis. The electrophysio- logy of the hypothalamic GnRH pulse generator in the rhesus monkey is reviewed more specifically by Knobil. In ovariectomized ewes, Clarke finds both positive and negative effects of estrogen on hypothalamic release of GnRH as well as on pituitary responsiveness to the peptide. Flerk6 et al.

This book discusses contemporary features of ject, creating, therefore, a lacuna the could be diagnosis of endocrine diseases using the filled by this project. radiologic technique of percutaneous venous This book is intended to be a practical guide blood sampling for hormone assay. A compre- for vascular and interventional radiologists, in- hensive survey of the field is provided by the ternists, surgeons, endocrinologists, and other contributing authors, who have considerable physicians who care for patients with endocrine expertise in the subject. Some have published diseases. The intention is to provide a practical several articles in the literature; others have text covering anatomical data, clinical prob- extensive clinical experience. lems related to the diagnosis of the endocrine The approach to many of the endocrine dis- diseases, patient preparation for the sampling, eases has been markedly improved ~uring the blood sampling techniques, sample manipula- last two decades because of selective venous tion and storage, laboratory data, and clinical blood sampling, not only in the diagnosis of the significance of the hormone sampling and condition but especially in the precise localiza- assay. tion of the hormone-producing lesion and its clinical significance. Scattered informationbn venous blood sam- pling is available in the literature, but there is Renan Uftacker no comprehensive text dealing with the sub- Reingard Sorensen Contents Preface v Contributors xi 1 Selective Venous Sampling for the Differential Diagnosis of Female Hyperandrogenemia 1 Lathar Moltz and Reingard Sorensen Introduction ...1 Diagnostic Procedures ...2 Indications ...4 Anatomy and Anatomical Variations...

In the forty years since melatonin's isolation and characterization, a large and multifaceted database has accrued. This book documents the diverse research contributions of most of the major laboratories in the field of melatonin research, as presented in a special conference to mark the 40 year anniversary of the isolation and chemical identification of this hormone. In addition, many chapters by younger scientists provide an exciting glimpse of where melatonin research is heading in the future.

Muscarinic acetylcholine receptors have played a key role in the advancement of knowledge of pharmacology and neurotransmission since the inception of studies in these fields, and the effects of naturally occurring drugs acting on muscarinic receptors were known and exploited for both therapeutic and non-therapeutic purposes for hundreds of years before the existence of the receptors themselves was recognized. This volume presents a broad yet detailed review of current knowledge of muscarinic receptors that will be valuable both to long-time muscarinic investigators and to those new to the field. It describes the detailed insights that have been obtained on the structure, function, and cell biology of muscarinic receptors. This volume also describes physiological analyses of muscarinic receptors and their roles in regulating the function of the brain and of a variety of peripheral tissues. This volume shows how the study of muscarinic receptors continues to provide new and surprising insights not just to the cholinergic system but to the broad areas of neurobiology, cell biology, pharmacology, and therapeutics.

Stjarne: The present review puts the emphasis on two important developments: the discovery that individual postganglionic sympathetic neurons may secrete multiple transmitter substances from different classes of vesicles and by different mechanisms, and the introduction of new techniques which may permit for the first time direct impulse by impulse analysis of transmitter secretion in individual sympathetic nerve varicosities. Illes: Exogenous and endogen opioid peptides elicit a number of effects in the organism, usually by modifying the function of transmitter and hormone systems, for example, activation of multiple opioid receptors. The effects of opioids on transmitter and hormone release have frequently been reviewed. This review gives a detailed overview on the involvement of multiple opioid receptors in these processes. Rothstein: This article gives an overview of the exchange in acidification and transepithelial salt and water transfer in nonepithelial cells. Delineating the exchanger's most important, common features, and concentrating particularly on its role in cell pH and volume regulation.

This book explains the treatment of endocrine disorders using natural therapies. Donald Beans provides the reader with everything there is to know to treat endocrine disorders without hormones. This book outlines the function of the endocrine glands and the testing of their function including clinical laboratory evaluation and bedside diagnosis. This is the first book to include the entire endocrine system and many natural therapies in one text, thus allowing the practitioner an unprecedented insight into endocrine treatment. Integrative Endocrinology discusses, in depth, the fundamental philosophical difference between hormone replacement therapy and integrative endocrinology. Natural therapies include acupuncture, gland cell therapy, homeopathy, herbal medicine, and a number of other methods. This book is of great value to health professionals, students and scholars in integrative medicine, alternative medicine and endocrinology. It is also valuable as a self help handbook for the motivated non-professional.

In September, 1977, at a conference organized by Dr. Kenneth McKerns in Northeast Harbor, Maine, USA, I was asked by the Editorial Committee of the Biochemical Endocrinology series to investigate the possibility of organizing the next meeting in France. I proposed a subject which is in the area of my research interest, and this subject was accepted. On arriving back in France, I first looked for an appropriate place for the meeting, and the Chateau de Seillac was chosen in accordance with many objective criteria. We know that all who attended the meeting held in Seillac enjoyed this quiet and charming place in the Loire Valley. The next step was to choose some experts in the field who would contribute to the monograph and present their papers at a conference for the purpose of generating discussions. The action of the local committee, composed of Dr. A. Tixier-Vidal, Dr. Claude Kordon, and me, was crucial in this respect. The local committee proposed the program for the meeting and a list of the majority of contributors to be invited. I wish to thank Dr. Tixier-Vidal and Dr. Kordon for their invaluable assistance.

Dr. Robert Volpe and his distinguished contributors comprehensively review the latest thinking about the theoretical, experimental, and clinical aspects of autoimmune endocrine disorders. These world-renowned experts examine the pathogenesis and immunogenetics of these diseases, discuss the role of sex hormones in autoimmunity, and elucidate the nature of autoantigens. They also provide clinical detail on a wide variety of autoimmune endocrinopathies, including autoimmune thyroid disease, Graves' ophthalmopathy and dermopathy, human insulin-dependent diabetes mellitus, and autoimmune adrenocortical failure. Postpartum autoimmune endocrine syndromes, autoimmune hypophysitis, and the polyglandular autoimmune syndromes are also discussed in detail. Comprehensive and authoritative, Autoimmune Endocrinopathies provides today's most up-to-date understanding of the etiology and pathogenesis of autoimmune endocrine diseases.