The cytochemical bioassay system was described in a short abstract in 1971, and more fully, in the cytochemical bioassay of corticotrophin, in 1972. Since then, cytochemical bioassays have been described for several polypeptide hormones, and these assays are already widely used. It is expedient that the subject should be reviewed, as it is in this monograph, by one writer who has had the good fortune to have taken part in the growth of cytochemistry from its early origins to its present position as the basis of possibly the most sensitive bioassay system currently available. However, it should be noted that major contributions have been made by many, both to the development of the subject and to the establishment of the bioassays. The object of this preface is to try to give some perspective to the growth of this subject and to record that the cytochemical bioassay system has been fostered by many outstanding scientists in an atmosphere of remarkable goodwill. To begin with, there could have been no cytochemical bioassays until cytochem istry had been converted from its rather unsure origins into a precise and quantitative form of cellular biochemistry. This was done with skill and enthusiastic dedication by my colleagues, Dr. Lucille Bitensky, Dr. F. P. Altman, Dr. R. G. L. W. Poulter and Mr. A. A. Silcox, first at the Royal College of Butcher, Dr."

For many years, patients who complained of prostatism had only a few treatment choices. The patient was either a candidate for an elective prostatectomy, or the operation was deferred until the patient became more symptomatic. The present text summarizes the multiple options which have become available to the practicing urologist. Minimally invasive techniques such as transurethral incision of the prostate, balloon dilatation, hyperthermia, laser therapy, and prostatic stents are described. Medical treatment with alpha-blockers, 5 alpha-reductase inhibitors, and flutamide are addressed by authors who have had extensive clinical experience with the use of these agents.

Traditions are dangerous; doubly so in science. Traditions are unchanging; science is about change. This was the 4th International Colloquium on Carbohydrate Metabolism in Pregnancy and the Newborn to be held in Aberdeen, and by now the form is set. How much its content has changed is a matter of nice judgement and not under the control of the organizers. It is not within their power to bring news of revolution, if there has been no revolution. Certainly many of the speakers had kent faces from previous Aberdeen meetings, but so they would be at any meeting on diabetes anywhere in the world. The written proceedings of scientific conferences have purposes other than to record changes: sometimes they need to state a consensus. The 3rd Colloquium came to an agreement about the importance of prepregnancy recognition and control of abnormalities of carbohydrate metabolism. The 4th set out to examine what results it had achieved. Much of this book is taken up with follow-up studies of the applications of similar regimes in different parts of the world. Since the first Aberdeen meeting in 1973, progress in the manage ment of diabetic pregnancy has been slow and steady, but the change in the city and the society where the meetings took place has been fast.

Endocrine Neoplasia is a comprehensive, updated, and clearly-written text covering the diseases for which endocrine surgical expertise is often needed. We look towards advances in the science and the art of endocrine surgery to continuously improve outcomes for our patients. The goal of this text was to provide a detailed description of both the underlying science of disease as well as the art of clinical management.

The book is divided into five sections addressing neoplasms of the thyroid, parathyroid, adrenal gland, neuroendocrine pancreas, and multiple endocrine neoplasia. Experts from the United States, Canada, and Australia have contributed chapters addressing both the biology of endocrine tumors and the clinical management of disease. Recent discoveries regarding the genetic underpinnings of disease are highlighted. Updated consensus guidelines were used for clinical recommendations. The management of complex and often confusing clinical problems is discussed in detail.

The unraveling of our knowledge of the functions of the adrenal gland constitutes one exciting development of modern medicine and biochemistry. We owe these advances to the felicitous cooperative efforts of the clinical investigator and the biochemist. Three centuries elapsed between the first recorded anatomical descrip tion of the adrenals and the demonstration by Dr. Addison in the mid-nineteenth century of the fatal results of the destruction of these glands by disease. It became evident from this observation that the adrenals secreted a "factor" or "factors" essential to life. It took approximately 90 years to isolate this elusive vital factor - cortisone - from beef adrenal cortices, independently by both Reichstein and his co-workers in Basle and Kendall and his group in the United States and another 10-15 years before it became more generally available for experimental and clinical use. It is perhaps difficult to believe that as recently as 35-40 years ago, before cortisone and cortisol were clinically available, the surgical removal of a benign adrenal cortical tumor in patients with Cushing's syndrome was associated with a prohibitive postoperative mortality rate. Within 12-36 h after operation, most of such patients developed an intractable state of shock, which was not manifested by significant electrolyte abnormalities or hypoglycemia and was unresponsive to the usual treatment for shock plus the generous use of salt-retaining hormone.

Reevaluation of tumor classification, differential diagnosis and differential therapy based on modern knowledge. Revision of all chapters to incorporate new facts based on recent discoveries.

The breadth of research efforts represented by the many excellent papers in these proceedings is an eloquent testimonial to the idea of one man Dr. Josiah Brown-to whose memory this volume is dedicated. His tragic and unexpected loss in a swimming accident in August 1985 brought to an abrupt close a long and distinguished career as a physician and scientist. The possibility of using fetal pancreas tissue for transplantation into insulin-deficient diabetic recipients had intrigued Dr. Brown for several years prior to 1972, when he began in earnest to assemble a research team to explore this idea in detail. He felt that improvements in the formulation and administration of insulin (even the later recombinant human insulin) had taken us about as far as we could go in treating diabetes, and that methods for achieving complete cures must be explored. Numerous advantages of the fetal pancreas quickly became apparent, and were explored scientifically by Dr. Brown and his group. Transplanted pancreas tissue from a fetal donor of the appropriate developmental stage engrafts quickly, and can reverse diabetes very efficiently (1-3). By shunting the venous'drainage of the graft into the hepatic portal vein, a single pancreatic rudiment can, in time, provide enough insulin to restore normoglycemia and urine volume in a diabetic adult recipient (4). As with fetal pancreas rudiments in culture, transplanted fetal pancreas tissue loses its exocrine character, while continuing to develop and maintain endocrine function.

Endocrine glands may be involved in patients with thalassemia major. In the last 20 years, new therapies have significantly improved life expectancy, while several endocrine abnormalities have been described in children, adolescents, and young adults suffering from thalassemia major.
The practical objective of this book is to establish guidelines for the management of endocrine disorders underlying the various phases of thalassemic life. Internationally acknowledged experts give a state-of-the-art account of physiopathological and therapeutical approaches to endocrine disorders in thalassemia and focus on such topics as growth hormones, thyroid diseases, puberty, hypogonadism, diabetes, and bone metabolism.

The regulation of the organism has traditionally been ascribed to two distinct systems-the nervous and the endocrine. Though coordination between the two systems has been acknowledged, researchers and authors have tended to deal with them as comprising separate categories of cells involved in different activities. With this approach, a given regulatory mechanism would be evaluated as to whether it should be accounted for by nervous or endocrine functions. The past 15 years, however, have witnessed numerous important discoveries and conceptual developments concerning the morphological, physiological, and bio chemical relations between the nervous and endocrine systems. Advances in im munocytochemical studies have revealed that there are a wide variety of messenger substances that function in both regulatory systems. As a result, researchers have been stimulated to investigate neuronlike properties of endocrine cells and, con versely, endocrine or secretory features of neurons. It has thus become obvious that the rigidities in the classic criteria of neurotransmitters and hormones may rather impede further advances in these research fields. The activities of neurons are no longer evaluated simply in terms of EPSP, IPSP, and the release of classic trans mitters such as acetylcholine, noradrenaline, and GABA. Hormonal actions are no longer analyzed solely with regard to concentrations of classic aminic and peptidic hormones in the systemic blood circulation. The concept of the paraneuron, which we proposed in 1975, has become one of the theoretical bases for the development of this trend of study.

The past 15 years have witnessed a marked increase in attempts to identify safe and effective treatment alternatives to prostatectomy. This book is a review of the current therapeutic efforts in the management of patients with benign prostatic hyperplasia. It is presented by a group of highly regarded basic and clinical scientists with a major interest in prostatic diseases.
The information provided in this book is aimed at a wide audience including private practice and academic urologists, research fellows and doctors in postgraduate training, and basic scientists interested in prostatic pathology.

Reproduction is the origination of new organisms from pre-existing ones. Among more than 35 separated forms of reproduction including several types of gamogony, parthenogenesis, agamogenesis, fission and division, and plas motomy, the bisexual mode of reproduction via fertilization provides genetic variability that allows species to adapt quickly to competitive and constantly changing environments. Several excellent reviews and books have been written in the past to analyse the mechanisms of fertilization in different eukaryotic species. During the last few years, however, renewed attention has been paid to examining the process of oocyte fertilization at the cellular/molecular level not only within a single species/group but also through different phylogenetic lineages. As a result of this effort, knowledge of the molecular pathways used by oocytes and spermatozoa at fertilization has increased, but still many ques tions remain to be answered. Being aware of the necessity of providing an inte grated view of the process of fertilization, this book has been entirely devoted to reviewing the process of oocyte fertilization at the cellular/molecular level in two different and separated groups of eukaryotic organisms: protozoa and metazoan animals. The book is organized into six sections dealing with oocyte fertilization in protozoa, invertebrates, teleost fishes, amphibians, birds and mammals. These sections are followed by a summary/concluding chapter that provides a com parative overview of the process of fertilization in these groups of eukaryotes."

How to treat advanced prostatic cancer remains controversial, despite intense basic and clinical research investigating the pathogenesis and natural history of this unique cancer highly prevalent in elderly males. Nine experts were asked to meet and discuss the facts. This resulting monograph gives an overview of the available knowledge on all aspects of the subject. The objective evaluation and consensus opinion of the authors presented here set this book apart from other publications with conflicting viewpoints. For readers eager to obtain a comprehensive and balanced view of the thousands of clinical contributions and clear advice on the choices, this book is a must.

This study assembles current and new information on the mechanisms involved in intracellular calcium regulation and their actual or potential relationship to cellular calcium transport. Topics discussed in detail are calcium channels, cellular calcium extrusion, sodium/calcium exchange, calcium-binding proteins with special reference to the vitamin D-induced calbindin, calcium transport and disorders thereof. Each topic is introduced with an overview followed by research papers dealing with relevant topics in each category. New information deals with calcium channels which are not voltage-sensitive, the structure and function of the plasma membrane Ca ATPase, the role of the Na/Ca exchanger in intracellular Na and proton regulation, a comprehensive overview of calcium transport with quantitative analysis of the role of the intestinal and renal calcium-binding proteins, description of the structure and function of the calbindin genes, and identification of calcium transport defects in diabetes and hypertension. Readers will be brought up-to-date on current knowledge and concepts in this rapidly expanding field and be directed to the relevant primary and secondary literature.

The purpose of these volumes is to provide a reference work for the methods of purifying many of the receptors we know about. This be comes increasingly important as full-length receptors are overexpressed in bacteria or in insect cell systems. A major problem for abundantly expressed proteins will be their purification. In addition to purification protocols, many other details can be found concerning an individual receptor that may not be available in standard texts or monographs. No book of this type is available as a compendium of purification procedures. Receptor Purification provides protocols for the purification of a wide variety of receptors. These include receptors that bind: neurotransmit ters, polypeptide hormones, steroid hormones, and ligands for related members of the steroid supergene family and others, including receptors involved in bacterial motion. The text of this information is substantial, so as to require its publication in two volumes. Consequently, a division was made by grouping receptors by the nature of their ligands. Thus, in Volume One there are contributions on serotonin receptors, adrenergic receptors, the purification of GTP-binding proteins, opioid receptors, neurotensin receptor, luteinizing hormone receptor, human chorionic gonadotropin receptor, follicle stimulating hormone receptor, thyro tropin receptor, prolactin receptor, epidermal growth factor receptor, platelet derived growth factor receptor, colony stimulating factor recep tor, insulin-like growth factor receptors, insulin receptor, fibronectin receptor, interferon receptor, and the cholecystokinin receptor.

1.1 Mechanism of Action of Glucocorticoid Hormones The current model of glucocorticoid hormone action is summarized in Fig. 1. After synthesis, glucocorticoids are secreted into the blood stream and trans- ported to target cells where they bind with high affinity (K-1O-9M) and d specificity to the intracellular glucocorticoid receptor (GR) protein. The sub- cellular localization of hormone-free GR is still a controversial issue. However, most data support the idea that unliganded GR is in the cytoplasmic compartment or loosely associated with the nucleus (Picard and Yamamoto 1987; Gustafsson et al. 1987 and references therein; LaFond et al. 1988; Gasc et al. 1989). Upon ligand binding, GR is activated into a form capable of interacting with DNA. The mechanism of GR activation probably involves a conformational change and dis- sociation from nonreceptor components, e.g., the 90-kDA heat shock protein (hsp90: Pratt et al. 1988; Bresnick et al. 1989; Denis and Gustafsson 1989). The subcellular location of activated GR has been firmly established to be inside the nucleus. In vivo, the hormone-receptor complex interacts with specific DNA Activation r:::.. ~ qc [!3-GC ...&.GC~ j ~ ? , BIOLOGICAL EFFECTS " t , Active Protein , , ~Vl\lent.

This book originates from a symposium held at the London Hospital Medical College under the auspices of Applied Chromatography Systems Ltd. to discuss the place of HPLC in the endocrinology field. Many of the authors of the present book were speakers at this symposium. It seemed to us that many endocrinolo gists did not at that time fully appreciate the value of HPLC, and this book was designed to publicise the potential value of this technique. A survey of methods used in the steroid field Cp 185) confirmed the view that HPLC is not being used as widely, particularly in research described in clinical journals, as might be expected. We hope that this book will illustrate, albeit in a few selected areas of endocrinology, just how versatile and powerful a technique HPLC is, and en courage those who have not yet experienced it to have a go. The beginner does not need to buy expensive instrumentation - all that is required is a pump, injector, column and detector - the rest can come later! All the authors have practical experience in the use of HPLC in the particular area they discuss. All readers who discover apparent errors or who feel that the treatment of a topic of interest can be improved upon are encouraged to contact the editors. All criti cism, especially if constructive, is welcomed. We are still learning, and other peoples' experience is always valuable.

The field of human artificial reproductive technology (ART) is continually advancing and has witnessed significant changes since the inception of Louise Brown in 1978. Though Louise Brown herself was conceived after the trans fer of a blastocyst, there remain significant confusion and debate regarding the stage at which the human embryo conceived in the laboratory should be replaced in the mother. Developments in culture media formulations, leading to the introduction of sequential media, have brought the role of the blasto cyst in human ART back into the spotlight. It was due to this resurgence of interest in the niche of extended culture in human infertility treatment that the symposium on "ART and the Human Blastocyst" was held. of this meeting within this volume bring to the forefront The proceedings the main issues raised with the transfer of embryos at the blastocyst stage. It is evident from the chapters that follow that ART needs to be perceived as a continuum of procedures, each one dependent on the preceding one, and all equally as important as each other. That is to say, the development of a com petent embryo is ultimately dependent on the quality of the gametes from which it was derived. With regard to the oocyte, this then places the emphasis on the physician to use a stimulation protocol that both produces quality oocytes and does not impair endometrial function. Maintenance of gamete and embryo quality is the laboratory's role.

Changes in the allocation of healthcare resources have raised issues related to the efficacy and outcomes of medical therapy and how such factors may be measured. The questions associated with the quality of life and functional capability of patients with chronic health conditions have been of special interest. Endocrine disorders have the potential for disrupting the general health and well-being of affected individuals and their families; thus they warrant serious attention. This symposium was convened in November 1997 at Palm Beach Gardens, Florida, to bring together medical, behavioral, and social scientists. The meeting fostered the presentation and discussion of the most current clinical research on the effects of various therapies on a wide range of endocrine disorders from diabetes to adrenal insufficiency and growth hormone deficiency. The participants, all noted national and international experts in their fields, focused their attention on both the biomedical value and effectiveness of treatment, as well as on the impact such treatments have on psychological states such as mood and cognition. Many presentations specifically emphasized the quality of life (QOL) indicators that now regu larly appear in many research protocols and reports. The pioneering work of two clinical researchers was a major highlight of the meeting and an Award of Recognition was presented to Robert Blizzard, M. D. , and John Money, Ph. D. , for their innovative and insightful work in pediatric endocrinology and psychosexual development.

As I reflect on the evolution of this book, I am struck by the differences be tween my early conceptions and the final product. When I was first ap proached by Springer-Verlag regarding a monograph on my interests in the area of fetal lung development, I imagined that it would be relatively easy to summarize my contributions, plus the work of other investigators as needed for proper perspective. This rather naive idea was abandoned as I prepared my initial outlines for the monograph. I quickly realized that con tributions from my laboratory are not sufficient for telling the story of "hormones and lung maturation." The result of this decision is a longer and more heavily-referenced book than I originally envisioned. Although I have attempted to discuss in considerable detail most aspects of hormones and the fetal lung, I know with certainty that I have not in cluded all relevant references in each area. In most of these instances this reflects my impatience or lack of diligence, and I offer my apologies to those investigators whose work has been so omitted. In some situations published work has not been cited in a deliberate decision to limit the breadth of discussion or, rarely, due to my judgment of major shortcom ings in experimental design or execution."

The tridecapeptide neurotensin (NT) was first identified in bovine hypothalamic extracts and characterized by Carraway and Leeman (1973,1975,1976) and has subsequently been found in all classes of vertebrates (Carraway and Leeman 1976; Kitabgi et al. 1976; Kataoka et al. 1979; Langer et al. 1979; Reinecke et al. 1980a; Cooper et al. 1981; Grant et al. 1982; Carraway et al. 1982; Eldred and Karten 1983), many invertebrates (Reinecke et al. 1980 b; Grimmelikhuijzen et al. 1981; Price et al. 1982), and certain bacteria (Bhatnagar and Carraway 1981). It is distributed throughout the mammalian central nervous system (CNS) (Uhl and Snyder 1977 a, b), gastrointestinal tract (Sundler et al. 1977; Schultzberg et al. 1980), cerebrospinal fluid (CSF), adrenals, pancreas, and plasma (Fernstrom et al. 1980). When administered systemically, the peptide has a variety of effects such as hypotension, hyperglycemia, decreased gastric acid secretion, decreased gut motility, and altered secretion of anterior pituitary hormones (Leeman and Carraway 1982). NT apparently does not cross the blood-brain barrier in appre- ciable quantities; however, when administered directly into the CNS, it produces a number of physiological and behavioral effects. A burgeoning body of evidence supports the role of NT as a neurotransmitter or neuromodulator. Thus far, het- erogeneous CNS distribution, release of NT upon neuronal depolarization, satu- rable and specific binding of NT to receptors, and degradation by peptidases have all been demonstrated.

Upon wresting the control of the earth from the Titans, Zeus assigned the task of creating living creatures to two Titan brothers who had sided with him in the epic battle just concluded. Because Epimetheus, who had been endowed only with hindsight, had the first hand in this creation, all the good attributes were exhaus ted by the time the lion, the elephant and other animals were created. When the time came for the creation of man, there were precious few materials left to work with. Not surprisingly, man was made weak and naked. Prometheus took pity on this miscreation and gave man the use of fire. For this foresight, Zeus meted out horrible punishment, binding Prometheus to a rocky pillar in the Caucasas Moun tains and letting a vulture consume his liver daily. It seems to me that the ancient Greeks in their unfathomable wisdom under stood the essence of the evolutionary process very well. Had Escherichia coli of 200 million years or so ago been endowed with the foresight to anticipate the eventual emergence of and subsequent dominance by mammals of this Earth, they would no doubt have equipped themselves, in anticipation of the coming cer tainty, with the lac operon to deal with lactose in the suckling mammalian infant's gut. Had they been able to do so, the actual emergance of mammals would have exerted no selective pressure upon existing E. COLI."

Endocrinologic investigations during pregnancy have focused in the last decades on placental hormones, the maternal endocrine system and maternal fetal interactions. Less is known about the fetus itself and the interaction of fetal hormonal response and physiological parameters. In this book physiologists, pediatricians and obstetricians active in experimental studies in both physiology and endocrinology combine both aspects of investigations. Historical remarks on the endocrine development of the fetus are followed by observations of the hormonal control of the cardiovascular system. Basic mechanisms of fetal endocrine control such as brain development, fetal growth, fetal behaviour, and thermoregulation are given particular consideration. Finally, carbohydrate metabolism and the mechanism of parturition are outlined.

It is a truism that as we age there are a number of underlying physiological changes conspiring to alter our level of behavioral and cognitive function ing. Despite the inherent interrelatedness of these behavioral and cognitive changes, all too often the papers we read confine themselves to specific, isolated components of the developing process. Although exceptions nat urally exist, we believe that these exceptions should become rule. Although an integrated approach is important in all areas of adult devel opment, it is perhaps particularly germane in the study of atypical aging. Here, changes in overall functioning can occur in rapid succession, with the synchrony of decline between different subprocesses making it difficult to factor changes in one process from changes in another. For example, because changes in cognitive functioning co-occur with other dramatic changes in (motoric) response capacities, it is unclear how one can effec tively study changes in the ability to cognize independent of changes in the very mechanisms (ability to execute motor sequences) so often used to index cognitive performance."

It has been my privilege and pleasure during the past half century to participate in the unfolding of present-day concepts of the mammalian female reproductive cycles. When the studies recorded here began in the late 1930s it was already established that cyclic ovarian function is governed by gonadotropic secretions from the anterior pituitary gland, the "conductor of the endrocrine orchestra," and that in turn this activity is importantly dependent in some way upon secretion of estro gens and progesterone by the ovaries. Although a role of the nervous system was recognized for the reflex-like induction of ovulation in rabbits and cats and the in duction of pseudopregnancy in rats and mice, and although there was even some evidence of neural participation in ovulation in rats, a major central neural role in the female cycle of most species was not apparent. Gonadotropic fractions of pitui tary extracts having distinct follicle-stimulating and luteinizing activities in test ani mals had been obtained, and these respective effects had been fairly well charac terized. Prolactin was well known for its lactogenic activity, but its luteotropic role in rats and mice had yet to be revealed. The molecular structure of the several estro gens and progesterone was known, and they were readily available as synthetic pro ducts. The broad concept of ovarian-pituitary reciprocity appeared to be an accept able explanation of the female cycle, with the ovary in control through the rhythmic rise and fall in secretion of follicular estrogen.