Every year there are new and exciting developments in assisted human reproduction, but how much do we really know about the underlying causes of infertility? This volume explores recent progress in the understanding of the genetics of spermatogenesis and male infertility. Topics include fundamental advances and current problems in the development and function of the testis, an outline of clinical findings in male infertility and an overview of the role of the Y chromosome in male fertility. Comprehensive critiques of posttranscriptional control during spermatogenesis, mammalian meiotic sterility, and comparative genetics of human spermatogenesis from the perspective of yeast, Drosophila and mice provide a global overview of the field.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

Diagnosis and Management of Polycystic Ovary Syndrome is a comprehensive clinical reference work for primary care physicians, internists, general endocrinologists, obstetricians, gynecologists and students. PCOS is a common but frequently misdiagnosed disease. Many symptoms can be alleviated by early intervention and effective management.

Prominent endocrinologists are gathered to detail current research and treatment in this metabolic disorder, affecting a growing population. The chapters are comprehensive, providing cutting edge knowledge on pathogenesis, manifestations, diagnosis and treatment of PCOS. Each chapter will be concise concluding with cogent practice points.

The variety of medical issues presenting in PCOS patients result in late referrals or in- appropriate advice. This title will be a tool in a further understanding of the metabolic and genetic basis of PCOS, while providing management strategies.

During the past five to ten years, a variety of tools has been developed in the disciplines of both gene engineering, and molecular and structural biology. Some of these advances have permitted scientists not only to identify and characterize genes, but also to target these genes by disruption, thus eliminating their function in living animals, and to det- mine the biological responses to altered gene products. This has particular significance in endocrine systems, in which feedback mechanisms between the hypothalamus, pi- itary, and end organs are critical in normal physiology. Interpretation of the physiological significance, or the site of action of specific molecules in this context, has been difficult prior to transgenic technology. Major advances have occurred specifically in the areas of growth and development, and of reproduction. Coupled with analysis of naturally occurring mutations in humans, the use of transgenic animals and in vitro systems has recently allowed endocrinologists to understand the importance of specific thyroid hormone receptor isoforms in vivo, the molecular basis for generalized resistance to thyroid hormones via mutations in the nuclear receptor, and mechanisms for suppressing gene transcription. Previously designated "orphan rec- tors," such as steroidogenic factor-1, were demonstrated to have critical roles in dev- opment and reproduction. Other nuclear receptors-including those for thyroid hormone, estrogens, androgens, and progesterone-were shown to bind to coactivator and co- pressor proteins that modified their transcriptional activity, and contributed to the ce- specific effects of the hormones.

Internationally recognized experts, pioneers, and opinion makers in evidence-based medicine (EBM) provocatively recast endocrine policy and practice in the light of EBM philosophy and principles. The authors explain the past, present, and future of EBM; consider its practical implications for endocrinology; demonstrate what the "evidence base" is in EBM; and present illustrative case studies by practicing evidence-based clinicians. Highlights include essays on why cost-effective analyses are problematic, the contrast between clinical investigations and large randomized trials, the role of Cochrane reviews and meta-analyses, and the curriculum requirements for training evidence-based endocrinologists.

It has been over 40 years since the original report by Salmon and Daughaday demon strating that the ability of GH to stimulate sulfation of cartilage was mediated by a "sulfation factor. " In the ensuing decades, it has become apparent that this "sulfation factor activity" encompasses a complex system ofligands (IGFs), receptors, and carrier proteins that are, in tum, responsible for a wide array of cellular actions. The IGF system has been demonstrated to be critically involved in both intrauterine and postnatal growth, and to have important implications in cancer biology as well, owing to the ability of the IGFs to function in endocrine, paracrine, and autocrine modes and given the wide distri bution of IGFs in virtually every organ system. The contributions to The /GF System reflect the wide span of interest in the IGF system and its implications for normal and abnormal growth and metabolism. The chapters have been divided into four broad sections: I. Molecular biology of the IGF system; II. Bio logical actions of the IGFs; III. IGF physiology; and IV. Clinical aspects of the IGFs. We have made every effort to highlight the major contemporary themes in IGF biology, but as is inevitable in such a fast-moving field, perspectives will continue to change as new information is accumulated."

A critical review by prominent experts of both the cutting-edge of stem cell biology and the application of stem cells to endocrine diseases, including diabetes, infertility, and liver-associated metabolic disorders. The authors discuss current research to modify stem cells, develop an endocrine-like cell, and use adult bone marrow stem cells to treat autoimmune diseases, including endocrine-based autoimmune diseases. Topics of interest include a review of all stem cell subtypes and their characteristics, approaches to promoting endocrine development from stem cells, and evidence for endocrine cell function from stem cells. The authors also outline how best to develop preclinical studies that will determine the safety and efficacy of stem cell therapies for endocrine disorders.

Don P. Wolf and Mary Zelinski-Wooten provide a comprehensive review of the procedures and techniques used in assisted reproduction, as well as in nuclear transfer for both the treatment of human infertility and the propagation of animals. Combining the details of clinical application with the physiological facts of reproduction, the authors treat subjects such as the in vitro maturation of oocytes, embryo culture, intracytoplasmic sperm injection, and the process of nuclear transfer. Cutting-edge and wide-ranging, Assisted Fertilization and Nuclear Transfer in Mammals offers clinical ARTs practitioners, research scientists, those responsible for animal care, and students not only an informative historical perspective on the development of ARTs, but also updates on several of the more dynamic clinical areas, and a highly practical understanding of their applications.

Endocrine Replacement Therapy in Clinical Practice, an update of Hormone Repla- ment Therapy published by Humana Press in 1999, aims to assist the endocrinologist, gynecologist, pediatrician, urologist, general surgeon, neurologist, neurosurgeon, p- chiatrist, generalist, and trainee in management of their patients with hormonal defici- cies or altered hormonal synthesis or responses. Many new authors have added several new chapters, and all of the previous chapters have been updated. Endocrine testing used to diagnose endocrine disorders and monitor hormone replacement therapy is reviewed. However, detailed discussion of physiology and pathophysiology is not an aim of this book, and these topics are covered in other volumes on endocrinology. Although no one is considered an expert in all areas of endocrine replacement therapy, each of the authors here have extensive knowledge and experience in the management of patients with s- cific endocrine disorders requiring hormone replacement treatment. Although some differences of opinion exist among experts in replacement therapy, each writer has attempted to give a balanced, unbiased recommendation. When com- rable regimens exist, the authors have made this apparent to the reader who can then choose the best treatment for the individual patient. Cost, therapeutic effectiveness, and route of administration are all important considerations in making the final selection of replacement therapy.

Leading researchers and experienced clinicians join forces not only to illuminate today's understanding of the endocrinology of menopause, but also to provide a sound basis for its successful management. These seasoned experts review in detail the cardiovascular, bone, brain, and genitourinary changes that accompany menopause and spell out the risks, benefits, and alternatives of conventional hormone replacement therapy. Selective estrogen receptor modulators (SERMs), androgen replacement, calcium supplementation, and the role of phytoestrogens are also fully reviewed. Menopause: Endocrinology and Management offers practicing physicians a comprehensive understanding of the menopause process, as well as an evidence-based approach to optimizing treatment strategies for the challenging medical problems accompanying this important period in women's lives.

Until recently, endocrinology and critical care medicine were two specialties in medicine that were rather uncomfortable with each other and hence quite i- lated. Fortunately, these two 'alien' disciplines have joined forces in successful attempts to perform high quality research in order to clarify the unknown. By integrating endocrinology in critical care medicine, or vice-versa depending on the specialty of the observer, new experimental and clinical data on the complex endocrine and metabolic derangements accompanying non-endocrine severe i- nesses came available which generated important novel insights with relevant clinical implications. In addition, the state of the art diagnosis and management of primary endocrine diseases that represent life-threatening situations leading to ICU admission has been updated. This issue of Contemporary Endocrinology aims at compiling the new ?ndings. The book indeed covers both areas of 'Acute Endocrinology' that are often taking care of at very distant sites within hospitals. The ?rst part deals with the classical life-threatening illnesses caused by primary endocrine diseases such as thyrotoxicosis, hypothyroidism, acute adrenal crisis, acute calcium disorders, pheochromocytoma, severe hyper- and hypoglycemia . The second part looks at endocrinology from the ICU side, starting with a g- eral overview of the dynamic neuroendocrine and metabolic stress responses in the condition of intensive care-dependent, non-endocrine critical illness.

A panel of leading experts integrate the latest findings from basic and clinical science to create a comprehensive treatment of the processes by which the brain acts as an endocrine organ, not only to control hormonal functions, but also to maintain homeostasis and regulate behavior. The authors-recognized both as leaders in their fields and as skilled teachers-provide systematic coverage of the analytical, anatomical, functional, clinical, and pathological aspects of neuroendocrinology. Topics range from the interactions between the nervous and endocrine systems to the regulation of reproduction, development, metabolism, fluid balance, and biological rhythms. Neuroendocrinology in Physiology and Medicine offers an unprecedented marriage of clinical and basic knowledge that has been missing from classical neuroscience, endocrinology, and physiology texts. It will teach today's medical students and serve researchers as a valuable reference to this rapidly growing field.

In the past five years, so much additional progress has been made in ourunderstanding of both the basic and c1inical aspects of a wide variety of thyroid disorders that a second edition of Diseases of the Thyroid was considered a necessary addition to the Contem porary Endocrinology series. Fresh perspectives also seemed warranted, so we recruited new authors for many of the chapters and believe that this edition will provide the reader with further insights into the pathophysiology and c1inical presentation and treatment of thyroid disease. It inc1udes topics ranging from neonatal thyroid screening, thyroid dysfunction during infancy and childhood, peripartum thyroid disorders, thyroid disease in the elderly, and the c1inical relevance of the sodiurnliodide symporter (NIS) to the pathogenesis and treatment of nodular goiter, thyroid cancer, thyrotoxicosis, and hypothyroidism. The worldwide problem of iodine deficiency and its eradication is also discussed, along with environmental goitrogens and iodine-induced thyroid disease. I am indebted to all the contributors for their cooperation and expertise in providing their chapters in an extremely timely fashion, to Mr. Thomas Moore and Mr. Craig Adams from Humana Press for their expert assistance, and to Ms. Christine Archung for providing superb administrative assistance. Lewis E. Braverman, MD v CONTENTS Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Molecular Mechanisms of Nuclear Thyroid Hormone Action William W. Chin and Paul M. Yen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 Nongenomic Actions of Thyroid Hormone Paul 1. Davis and F aith B. Davis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 3 Thyroid Testing: A Clinical Approach Laurie A. Kane and Hossein Gharib . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

Distinguished clinician-scientists describe in concise studies their most difficult cases and reveal what they did, how they did it, and why. The cases cover a wide range of endocrine problems. Each case study reviews how the patient was managed, details the reasons why various tests and treatments-many only recently available-were carried out, and provides references to ensure that those novel methodologies can be easily translated into the endocrine specialist's daily practice. The authors provide practical solutions for these difficult-to-manage cases, and successfully apply knowledge fresh from the laboratory to decisions about patient management. Practical and stimulating, Challenging Cases in Endocrinology demonstrates for every clinical endocrinologist precisely how specialists approach their most challenging cases and how these approaches can be effectively applied in the daily practice of endocrinology.

The explosive growth in the field of molecular biology over the last two decades has started to make a great impact on clinical medicine. Genes have been cloned for diseases that were poorly understood only a decade ago. Additionally, investigators are increasingly aware that there are strong genetic components to complex disorders, such as osteoporosis, that are not classically thought of as genetic disorders. New insights into the pathogenesis of metabolic bone diseases have been obtained from investigations into the molecular biology of these diseases and new therapies will become available based on these new insights. In The Genefies of Osteoporosis and Metabolie Bane Disease, I have assembled an internationally renowned group of experts to write the various chapters. Each of the authors is an expert in his/her field who is currently performing research on the content of their chapter and have made important contributions to the understanding of the clinical fea tures and pathophysiology of metabolic bone disease and genetics. The first part of The Genefies of Osteoporosis and Metabolie Bane Disease addresses issues related to genetic contributions to the development of osteoporosis and the many factors that must be considered when searching for genesthat predispose to osteoporosis. The second sec tion addresses recent advances in the clinical and molecular biological aspects of inherited metabolic bone disorders. The last section reviews the latest techniques for finding genes that predispose to metabolic bone diseases.

This text is a review of current management techniques for pituitary tumors, incorporating recent advances and discussions by experienced clinicians. The use of both endocrinologists and neurosurgeons as chapter authors allows differing perspectives to be incorporated. The book is organized around individual tumor types, with additional chapter topics added for those subjects requiring special emphasis. Appropriate photographs and illustrations are incorporated as warranted.

Authoritative researchers and clinicians review our latest understanding of andrology in both basic science and clinical medicine. Topics range from explaining the biology of androgens-from several different perspectives-to illuminating their role in the development and modulation of physiologic systems. Authors demonstrate in a number of cases that testosterone can be a useful adjunct to the treatment of a variety of disease states. Other chapters consider important topics such as androgens use in athletes, the potential of androgens to improve physical function and quality of life in older men, and androgens as potential male contraceptives.

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."

Roger Cone and a distinguished team of expert investigators provide the first major treatment of this critically important receptor family. The book illuminates the structure and function of these receptors through a wide-ranging review of the latest findings concerning the biology, physiology, and pharmacology of their peptide ligands and covers the major melanocortin peptides, Melanocortin-1-Receptors through Melanocortin-5-Receptors. Topics include the characterization of the melanocortin receptors, the biochemical mechanism of receptor action, and receptor function and regulation. Timely and authoritative, The Melanocortin Receptors offers an up-to-date knowledge base on the remarkably complex structure and functions of the melanocortins, a guide that will prove invaluable for today's neuroscientists, endocrinologists, pharmacologists, and other clinical and experimental investigators working in this fast moving field.

There is currently no single book with up to date information on osteoclast function and bone resorption.

A useful collection of information, not readily available in a concentrated and convenient form on the market.

Provides a comprehensive overview of the field.

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.

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.

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.

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.

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.