Over the last decade it has been shown that orphan G protein-coupled receptors (GPCRs) can be used as targets to discover novel neuropeptides. A dozen neuropeptides have been identified through this approach. Each of these neuropeptides has opened new doors for our understanding of fundamental physiological or behavioral responses. For example the orexins, MCH and ghrelin carry fundamental roles in regulating food intake while neuropeptide S, neuromedin S, the prokineticins and the orexins are major players in modulating sleep and circadian rhythms. The chapters of this book review the latest research in the field, most of them are written by the original discoverers of the respective novel neuropeptide. Emphasis is set not only on their discovery but also on their functional significance. Since many of these neuropeptides are part of drug discovery programs, this book impacts academic as well as pharmaceutical research.

aintaining extracellular calcium concentrations within a narrow range is critical for the survival of most vertebrates. PTH, together with vitamin D, responds to hypocalcemia to increase extracellu M lar calcium levels, by acting on bone, kidney and intestine. The recent intro duction of PTH as a major therapeutic agent in osteoporosis has directed renewed interest in this important hormone and in the physiology of the parathyroid gland. The parathyroid is unique in that low serum calcium stimulates PTH secretion. As hypocalcemia persists, there is also an increase in PTH synthesis. Chronic hypocalcemia leads to hypertrophy and hyper plasia of the parathyroid gland together with increased production of the hormone. Phosphate is also a key modulator of PTH secretion, gene expres sion and parathyroid cell proliferation. Understanding the biology of the parathyroid as well as the mecha nisms of associated diseases has taken great strides in recent years. This book summarizes the molecular mechanisms involved in the function of the para thyroid gland. The first chapter reviews the development of the parathyroid gland and the genes involved in this process as identified using genetically manipulated mice. Then the biosynthetic pathway of PTH from gene ex pression to its intracellular processing and the sequences in the gene control ling its transcription as well as those regulating mRNA processing, stability and translation are described."

Skin lesions are often the first sign for an endocrine disease. Their description is thus of relevance for early diagnosis and treatment of endocrine disease for specialists in endocrinology as well as in dermatology.

Lavishly illustrated, this book describes the clinical and histological features of skin lesions observed in endocrine diseases. All features are reader-friendly structured and written in the language of dermatologists in order to enable a simple association between the features observed and the endocrine etiology.

Modern cardiovascular science has produced a revolutionary new idea: the heart acts not merely as a pump, but as a "gland," that is as a regulator of circulatory homeostasis and salt-water balance. This book combines the classical heamodynamic view with the new neuro-hormonal paradigm, in all its potential clinical implications. The book will interest physiologists and clinicians involved in the study of the cardiovascular system and care of heart patients.

Information gathered from cell-free systems, cell cultures, animal models, and human studies, together provide important insights to our understanding of hormonal cancer causation, development, and prevention; the primary objective of these Symposia. A special emphasis is placed on the two major endocrine-related cancers, that is, breast and prostate. The emerging fields of colon, lung, and pancreatic cancers in relation to hormones are examined.

Table 1 (Continuation) Reference Subject J. DAVIS, 1957, 1960b, 1961b, 1962b, 1963a; Regulation of secretion FARRELL, 1958; BARTTER et aI. , 1959; DENTON et aI. , 1959, 1960; COGHLAN et aI. , 1960; FOURMAN, 1962; MULRow and GANONG, 1962, 1964; WRIGHT, 1962; BLAIR-WEST et al. , 1963b; HOUDAS and FAVAREL- GARRIGUES, 1963 Relation of secretion to changes BARTTER, 1958 in intravascular volume Angiotensin (see Renin-angiotensin system) Blood volume and tonicity Regulation BLACK, 1954; E. BROWN et aI. , 1957; WELT, 1957; BARTTER, 1963; GAUER and HENRY, 1963 Receptors regulating SMITH, 1957 Oerebral cortex and cardiovascular function HOFF et aI. , 1963 Drugs affecting endocrine function GAUNT et al. , 1961 Erythropoietin JACOBSON, 1963; JACOBSON and DOYLE, 1963 Growth hormone (including action on adrenal cortex) FrnKEL, 1962 Hypertension Clinical and physiological aspects PAGE, 1962 SKELTON, 1959 During adrenal regeneration Renal (see Renin-angiotensin system) Russian work on SIMONSON and BROZEK, 1959 Juxtaglomerular cells Anatomy and physiology TOBIAN, 1960a, b, 1962, 1964; HATT et aI. , 1962; P. HARTROFT, 1963 Pineal and related organs KELLY, 1962 Comparative anatomy Renin-angiotensin system Chemistry, physiology, and structure- BRAUN-MENENDEZ et aI. , 1946; activity relationships BRAUN-MENENDEZ, 1956; BUMl'uS et aI. , 1961; SKEGGS, 1960; SKEGGS et aI. , 1957, 1964; PEART, 1959; GROSS and TURRIAN, 1960; PAGE and BUMl'us, 1961, 1962 Relation to hypertension in man WAKERLIN, 1955; GROSS, 1958, 1960, 1964; and animals Proceedings, Conference on Hypertension, 1958; KORNEL, 1959; TAQUINI and TAQUINI, 1961; GROSS et aI.

A Guide to the Practice of Paediatric Endocrinology concisely catalogs and analyzes the hormonal problems of children and offers practical guidance for their diagnosis and treatment. The author examines each of the endocrine glands and covers such topics as sexual development, growth, weight, puberty, thyroid disorders, adrenal disorders, salt and water balance, calcium balance, glucose homeostasis, and neoplasia. He then suggests practical procedures for managing ailments in each of these areas, including tests, imaging, and drug treatment, with specific information on normal values for the tests and guides to drug dosages. The volume is illustrated throughout with photographs and clear, informative charts. For all pediatricians and endocrinologists, this book will be a vital resource on hormonal disorders in children.

Experienced physicians concisely explain the pathophysiology and clinical manifestations of endocrine disorders and survey all the latest laboratory diagnostics. Topics range widely from an overview of the diagnosis of diabetes and the long-term monitoring of its complications to the evaluation of menstrual dysfunction. Coverage is also given to the diagnosis of pituitary tumors, Cushing's syndrome, thyroid disease, and hypoglycemia; the evaluation of endocrine-induced hypertension; the assessment of dyslipidemia and obesity; and approaches to diagnosing hyper- and hypocalcemia. There are also discussions of osteoporosis, hypogonadism and erectile dysfunction, and hyperandrogenism in women. The authors each review the complex physiological basis of the relevant endocrine processes and provide richly instructive recommendations for followup and long-term management of patients.

Now in a fully revised and updated fourth edition, this book remains the most comprehensive resource on Prader-Willi syndrome (PWS) available on the market. There have been significant changes in the diagnosis, clinical care and treatment of PWS since the previous edition was published in 2006, and more thorough information on understanding the cause and diagnosis of the condition, along with clinical presentation and findings with natural history data now available. The book is divided into three thematic sections. Part One discusses the genetics, diagnosis, research and overview of PWS, including current laboratory testing. The medical physiology and treatment of PWS comprise Part Two, covering the GI system, obesity as well as the use of growth hormone. Part Three, the largest section, presents a wide-ranging, multidisciplinary management approach to PWS, attending to the many manifestations of the condition. Topics here include neurodevelopmental aspects, speech and language disorders, motor issues, psychological and behavioral management, educational and transitional considerations, vocational training and residential care, and advocacy for both school discipline and sexuality. Syndrome-specific growth charts, benefits eligibility information and additional resources are included in helpful appendices. Timely and well-crafted, this latest edition of Management of Prader-Willi Syndrome remains the gold standard for clinicians and health care providers working with patients diagnosed with this rare obesity-related genetic disorder.

The field of androgen excess disorders has advanced substantially since the original publication of this book. The Androgen Excess Society (AES) was founded to bring together investigators in the field. A better understanding of the screening, progression, and molecular genetics of nonclassic adrenal hyperplasia (NCAH) has improved the clinical care and diagnostic accuracy of these patients. New criteria for the diagnosis of the polycystic ovary syndrome (PCOS) were proposed in Rotterdam, criteria that have resulted in controversy and, hopefully, initiation of new studies. The association of insulin resistance with PCOS has been strengthened, and the role of metformin in tre- ing the infertility of the PCOS has been validated. Risks for diabetes and, more cont- versially, cardiovascular disease in women with PCOS have received substantial investigation. Our understanding of the epidemiology and economic impact of these disorders has expanded, emphasizing their critical importance. These are but a few highlights of how the terrain has changed in a relatively brief period of time. In keeping with these advances, the title of this book has been revised to reflect the growing importance of PCOS as the most prevalent androgen excess disorder in women, and arguably, as the one that might have the most serious adverse consequences for general health. There are fewer chapters to provide a more focused elucidation of the area. Several chapters were penned by new (and young) authors who are conducting cutting-edge research in the field.

In Adrenal Disorders, a panel of distinguished physicians and researchers select the most relevant new findings and integrate them into the existing body of clinical knowledge on adrenal pathologies. The book includes important reviews of disturbances in cortisol homeostasis, and new concepts regarding adrenal tumors and hereditary adrenal diseases. Also discussed are mineralocorticoids and the syndromes of mineralocortoid excess and aldosterone synthase deficiency. Authoritative and insightful, Adrenal Disorders provides physicians and scientists with a comprehensive, state-of-the-art practical guide to the devastating diseases of the adrenals that are so often difficult to diagnose and treat.

A large number of chemical agents are known which affect blood and blood-forming organs. The purpose of this volume is to review the sig- nificant advances made over the past several years regarding such chemical agents. The purification, biological action, and therapeutic implications of several widely used hematopoietic growth factors such as interleukin 3 (IL-3 or multi-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), colony stimu- lating factor (CSF-I or M-CSF), thrombopoietin, and erythropoietin are included in this volume. These factors are important in regulating several hematopoietic cell lines such as neutrophils, monocytes, eosinophils, macrophages, megakaryocytes, platelets, and erythrocytes. People are exposed daily to numerous toxic chemical substances present in our environment which produce a suppression of erythropoiesis, myelo- poiesis, lymphocytopoiesis, and megakaryocytopoiesis. Attempts have been made in this volume to assess the therapeutic role of some of the hematopoietic factors such as erythropoietin in the anemia of end stage renal disease, as well as colony stimulating factors in other hematopoietic abnormalities. In addition, some of the chemical factors in our environment which suppress major hematopoietic lineages stimulated by erythropoietin, macrophage colony stimulating factor, granulocyte colony stimulating factor, interleukin I-alpha, interleukin I-beta, and interleukins 2, 3, 4, 5, 6, 7, and 9 are also included. An updating of the mechanism of action of each of these factors on the major hematopoietic lineages is covered.

Both thyroid dysfunction and heart failure show a high prevalence in the adult population. Frequently, in clinical practice, a multidisciplinary approach is useful to optimize the management of patients with these conditions. Although there is no doubt regarding the close link between cardiovascular pathophysiology and thyroid homeostasis, our understanding of this association is far from being exhaustive. Thyroid hormone regulates the expression of cardiac-specific functional contractile and structural proteins and plays a pivotal role in modulating both diastolic and systolic function as well as peripheral vascular resistance. The close relationship between thyroid and heart dysfunction is strongly supported by recent evidence demonstrating that an altered thyroid profile is a negative prognostic predictor in patients with heart failure. The treatment of chronic heart failure, especially in advanced stages of the disease, continues to be an open and challenging field. The potential of novel thyroid hormone therapies that address the molecular biology of thyroid dysfunction and heart failure thus represents an attractive area of multidisciplinary scientific interest. This book is a readable, integrated, and highly up to date presentation of the clinical, pathophysiological, and basic science aspects of thyroid-heart failure interactions. It addresses a complex subject in an approach that targets a large audience of readers.

This book provides an up-to-date overview of the role of neurosteroids and neuroactive steroids in the regulation of brain processes and neuropsychiatric disorders. It addresses the neurosteroid function in brain development and plasticity, in both the normal and the pathological brain. It also suggests possible therapeutic approaches to the use of natural occurring or sinthetic neurosteroids. The contributors suggest that neuroactive steroids could have a role in clinical practice.

A definitive review in the field of magnesium research, this book brings together the proceedings of the 11th International Magnesium Symposium in Osaka, Japan from October 22-26, 2006. Written by authorities in the area, the book provides a thorough overview of progress in the area of magnesium research. The author is one of the world's foremost magnesium researchers and reviewers, and the book provides essential reading for researchers in magnesium.

Latest issue in the CURRENT TOPICS IN NEUROENDOCRINOLOGY se- ries which has been gaining a great deal of reputation as a primary source for reviews in neuroendocrinology and related areas in the past few years.

Lactogenic hormone activity was first observed in bovine pituitary extracts by Stricker and Griiter in 1928, working in Bouin's laboratory in Strasbourg. Since that time prolactin has been shown to exist in anterior pituitary extracts of almost all vertebrate species investigated. Although its biology was extensively studied in many mammalian species, the existence of prolactin in the human was generally doubted, despite the positive evidence produced by such researchers as Pasteels. This can partly be explained by the fact that human growth hormone isolated in 1961, is itself a potent lactogen, in contrast to nonprimate growth hormones, and is present in the normal human pituitary in much greater amounts than prolactin. As a result there was a lag of nearly 10 years until prolactin was unanimously accepted as a hormone of the human pituitary, separate from human growth hormone. In 1970 new bioassay techniques permitted the demonstration of prolactin bioactivity in the serum of postpartum women and galactorrhea patients, and chromatographic methods led to the isolation and purification of human prolactin allowing the establishment of a specific radioimmunoassay for this hormone. This opened the road to the understanding of prolactin physiology and pathophysiology in the human, which has revolutionized clinical neuroendocrinology and reproductive endocrinology. Particularly hyperprolactinemia has turned out to be one of the most common endocrine syndromes.

Congenital adrenal hyperplasia (CAH) consists of a group of disorders of adrenal steroidogenesis. Each disorder results from an inherited deficiency of one of the several enzymes necessary for normal steroid synthesis. The different enzyme deficiencies produce characteristic patterns of hormonal abnormalities; the clinical symptoms of the different forms of CAH depend on the particular hormones that are deficient or that are produced in excess. The earliest documented description of CAH was by DeCrecchio in 1865 (DeCrecchio 1865). This Neapolitan anatomist described a cadaver having a penis with first degree hypospadias but no externally palpable gonads. Dis- section revealed a vagina, uterus, fallopian tubes, ovaries, and markedly enlarged adrenals. It is interesting that the subject suffered a confusion of sex assignment, being declared a female at birth and a male 4 years later. He conducted himself as a male sexually and socially. Since the original descrip- tion of this case, investigators have unravelled the pathophysiology of the inborn errors of steroidogenesis. 1 Steroidogenesis and Enzymatic Conversions of Adrenal Steroid Hormones A. Steroidogenesis The adrenal synthesizes three main classes of hormones: mineralocorticoids (17-deoxy pathway), glucocorticoids (17-hydroxy pathway), and sex steroids.

The European School of Oncology came into existence to respond to a need for informa tion, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Univer sities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.

In the past 10 years hirsutism has been the object of a considerable number of fundamental studies. It provides endocrinologists with an experimental model for the investigation of androgen secretion, metabolism and mechanism of action. Plasma androgen assay, free testosterone measurement, hepatic and extrahepatic androgen metabolic clearance and androgen metabolism in the skin are the different steps which were studied by many groups and represent valuable parameters of the mechanisms of hirsutism. Determination of the origin of androgen oversecretion has become easier by technical progress in differential effiuent venous catheterism, which makes it possible to compare androgens in adrenal or ovarian effiuent veins to their peripheral levels, and to determine the ovarian or adrenal source of the androgen oversecretion as well as the side responsible, essential in the case of tumors. The study of androgen metabolism and the discovery of androgen receptors in the skin confIrm the latter as an actual target cell for androgens. This target cell uses the circulating active androgen, i. e., testosterone and can also metabolize local inactive androgens into active ones. This is the case of androstenedione and dehy droepiandrosterone which are the two main androgens secreted in women, since women secrete very little testosterone. The capacity of the skin to transform inactive androgens into active ones varies from one individual to another. That would support the concept of variable skin receptivity from one woman to another and from one ethnic group to another."

The physiology and metabolism of thyroid hormones were areas of intense research investigation during the 1970s. Radioimmunoassays were applied to study the concentration of iodothyronines in biologic fluids. These techniques proved to be highly sensitive, specific, and reproducible as well as rapid. The availability of specific radioimmunoassays led to the detection of several iodothyronines in human biologic fluids, e. g., reverse triiodothyronine (rT 3), diiodothyronines, monoiodothyronines, and acetic acid derivatives of thyroxine (T 4) and T 3, which were previously either unknown or briefly considered but forgotten in the 1950s. This monograph is intended for readers who desire an overview of thyroid hormone physiology as it was understood in 1979. It should be especially useful to trainees in endocrinology and individuals interested in potential research projects. The main focus has been on the studies conducted between 1969 and 1978, alt lOugh other information has been reviewed to provide an overall working knowledge of the field. A list of over 500 references, although probably still incomplete, should lead a reader to at least a few important articles in each area relevant to thyroid hormone physiology.

As far as we are aware, this is the first attempt to cover the com parative physiology of the pancreatic islets in a monograph. The topics discussed would probably have sufficed to fill about half a dozen monographs, a matter that becomes obvious from a look at the Contents. Hence, we have tried to present the ma terial more in the form of a digest, to emphasize evolutionary perspectives, to point out critical issues, and to identify challenging topics for future research. This approach required an arbitrary reduction of the num ber of references, and we therefore join the chorus of recent authors who beg their colleagues for understanding if some of their publications do not appear in the bibliography. Keeping up with the current literature was like fighting one of those monsters that grow a couple of new heads for each one that is cut off. Nevertheless, we hope that we have covered most of the key publications up to the autumn of 1986. We gratefully acknowledge the advice of many colleagues, and in particular the invaluable criticisms of Robert L. Hazelwood and Erika Plisetskaya. Special thanks are due to the series editor, Donald S. Farner, for his patience and guidance, both of which were fresh proof of his legendary diplomatic skills. Finally, we wish to thank Dr. D. Czeschlik and his staff at the Springer Verlag for their patience and support. Philadelphia, PA AUGUST EpPLE Greenville, NC JACK E. BRINN September 1987 v Contents Chapter 1. Introduction .......................... ."

The term polycystic ovary syndrome (peOS) is meant to describe a clinical endocrinopathy characterized by menstrual irregularity and evidence of hyperandrogenism. While recognized since the 1800s, a clinical composite was not constructed until 1935 when Stein and Leventhal reported their findings of seven women with infertility, menstrual dysfunction, hirsutism, and enlarged ovaries. Notably, the ovaries contained numerous multiple cysts and the ovarian capsule was thickened. At the time, this preciseness of definition was sufficient to entitle the entity Stein-Leventhal syndrome. Subsequently, over the intervening years as investigators attempted to un ravel the pathophysiology and genesis of this disorder and the number of reported studies increased, there ensued a gradual and distinct terminologic conversion to polycystic ovary syndrome, which, whether intentional or not, connoted a less well-defined condition. Perhaps this is appropriately so, given the seemingly broadening spectrum of clinical presentations and the continuing debate over what constitutes peos. The expansive new knowledge about peos was discussed to a significant degree at an international symposium organized by Serono Symposia USA and held in Boston in the late spring of 1995. Ovarian physiology, including the fate of the follicular unit, was a central focus with several presentations on the genesis, growth, and death of ovarian cellular components. A discus sion of the regulation of ovarian cell function was also highlighted and comprised a major portion of the program."

The various congresses on growth hormone (GH) which have been held in Milan since 1967, the Milan Congresses, have witnessed over 25 years the tremendous expansion of a research field that was based initially upon the scarce knowledge of the biological properties of a protein. GH, whose chemical structure had just been identified and a radioimmunoassay developed for its measurement in blood, became in the following years a major area of biological research. The boundaries have since become blurred, as the research area has extended to the physiology and pathology of growth, puberty and reproduction, and the control of metabolism during the whole lifespan. Since the last GH Congress held in 1987, GH studies using the molecular biological approach have resulted in the puri fication, cloning and expression of the human GH (hGH) recep tor and binding protein, in new and exciting information on the insulin-like growth factors (IGF) and their paracrine and autocrine roles, and in the awareness that a panoply of binding proteins are present in the extracellular fluids and can, possibly, modulate IGF-receptor interactions and, thus, IGF actions. Finally, the availability of large amounts of biosynthetic hGH, besides allow ing more extensive clinical use in states of GH deficiency and extrasomatotrophic pathologies, has permitted disclosure of im portant metabolic effects of hGH during adulthood and, perhaps, aging and in many protein catabolic states."

It is fourteen years since insulin was last reviewed in The Handbook of Ex perimental Pharmacology, in volume 32. The present endeavor is more modest in scope. Volume 32 appeared in two separate parts, each having its own subeditors, and together the two parts covered nearly all areas of insulin pharmacology. Such comprehensiveness seemed impractical in a new volume. The amount of in formation related to insulin that is now available simply would not fit in a reasonable amount of space. Furthermore, for better or worse, scientists have be come so specialized that a volume providing such broad coverage seemed likely in its totality to be of interest or value to very few individuals. We therefore decided to limit the present volume to the following areas: insulin chemistry and structure, insulin biosynthesis and secretion, insulin receptor, and insulin action at the cellular level. We felt these areas formed a coherent unit. We also felt, perhaps as much because of our own interests and perspectives as any objective reality, that these were the areas in which recent progress has been most dramatic, and yet, paradoxically and tantalizingly, these were the areas in which most has yet to be learned. Even with this limited scope, there are some major gaps in coverage. Regrettably, two important areas, the beta cell ATP-sensitive potassium channel and the glucose transporter, were among these. Nevertheless, the authors who con tributed have done an excellent job, and we would like to thank them for their diligence.