In 2001 we wrote the book Graves' Disease: A Practical Guide (McFarland), which described the causes, diagnosis, treatment and disease course of Graves' disease and other hyperthyroid disorders, such as toxic multinodular goiter, thyroiditis, resistance to thyroid hormone, and hyperthyroidism caused by medications and genetic mutations. The present work continues the above but focuses on subsequent advances in disease pathology, including discoveries regarding the genetic, immune system, and environmental factors that lead to hyperthyroid disorders; new guidelines for conventional treatment; and alternative and complementary medical therapies are included. Additional sections describe special circumstances such as hyperthyroidism in pregnancy and in children, and transient hyperthyroidism in the newborn.

This third installment of The Year in Diabetes and Obesity review series includes reviews with a special focus on metabolic syndrome and health. NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit http://ordering.onlinelibrary.wiley.com/subs.asp?ref=1749-6632&doi=10.1111/(ISSN)1749-6632. ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to Annals online and discounts on print volumes. Please visit http://www.nyas.org/MemberCenter/Join.aspx for more information about becoming a member.

In a rapidly evolving and extremely important area of medical science, it is often difficult for the student, teacher, and researcher to keep abreast of all the important advances. The purpose of Molecular Biology ofDiabetes, Parts I and II is to bring to these individuals the latest knowledge of diabetes-related research in a comprehensive, yet concise manner. To this end, we have assembled chapters, written by most of the world's experts in the field, that we believe compre hensively survey and synthesize a coherent understanding of the subject. Studies of the etiology of type I and type II diabetes are extremely exciting and essential, since we hope to one day prevent the disease using gene therapy. These aspects are covered in Molecular Biology of Diabetes: I. Autoimmunity and Genetics; Insulin Synthesis and Secretion. In type II diabetes, an abnormality in pancreatic secretion exists concomitantly with peripheral insulin resistance. This abnor mality of insulin secretion is believed to be related to a defect(s) in glucose sensing. Uncoupling of glucose sensing from insulin secre tion may be the crucial step in the pathogenesis of noninsulin-depen dent diabetes. In this volume, we have invited authors to describe their studies on all known factors affecting ~-cell function, including autoimmunity and genetics of diabetes, as well as molecular mecha nisms of insulin synthesis and secretion. In the last few years, the most rapidly advancing area of research in diabetes has been, in fact, related to insulin action.

Embryoimplantationisaremarkableandcomplexprocess. Approachesde- velopedfromthefieldsofcellanddevelopmentalbiology,immunology, andmolecularbiologyhavegreatlyenhancedourabilitytostudythe sharedaswellasuniquefeaturesofembryo-uterineinteractions. Impres- siveandcriticalgroundworkhasbeenlaidbyalargeanddedicatedarray ofendocrinologists,reproductivebiologists,andanatomists. Thesestudies havesetthestagetoutilizesensitiveandsophisticatedtechniquestode- tectandmodulateproteinandgeneexpression. Justasthesymbiosisofmother andfetusiscriticalforthemaintenanceofpregnancy,soisthesynergyamong investigatorsfrommanydisciplines,bothinbasicandclinicalarenas,keyto unravelingthemysteriesofimplantationandplacentation. Alargegroupof contributorsinthisfieldhadtheopportunitytomeetanddiscussthestateof thisartwiththesupportofSeronoSymposiaUSA,Inc. Whileitisneverpos- sibletobringtogethereveryonewhohasplayedanimportantrole,itwas, nonetheless,bothexcitingandgratifyingtohavesomanycolleaguestogether forthisevent. Inthechaptersthatfollow,thehighlightsofthismeetingarepresented assummarizedbytheindividualpresentersofsevendifferentsessions. The topichasbeenconsideredfromthebroadsocialandethicalimplications ofmoderninvitrofertilizationandassistedreproductivetechnologiesto detailedmolecularcontrolsovereventsthatoccurduringembryonicdevel- opment,uterinepreparationforimplantation,andplacentalorganogenesis. Thesechaptersdemonstratethesignificantandrapidprogressbeingmade inthisfieldofbiologyandmedicine. Atthesametime,theyshowthat muchmoreneedstobedonetounderstandandfullyappreciatethispro- cess. Lessonslearnedfromthiseffortcanbeexpectedtocontinuetopro- videinsightsintoother,relatedfields. Ofthemanycontributorstoour understandingoftheprocessofimplantation,nonehavehadalargerim- pactthanourcolleague,AllenEnders. Dr. Endershasplayedaparamount roleindevelopingthebasicunderstandingofthecellbiologicalprocesses vii VIII Preface underlyingimplantationandplacentationinmanyspecies,includinghu- mans. Hecontinuestocontributeandguidethoughtintheseareas. The participantsofthissymposiumrecognizedDr. Enders'impressivecontribu- tionsbyholdingthiseventinhishonor. DANIELD. CARSON * Contents Preface vii Contributors xiii PartI. Development and Future ofHuman In Vitro Fertilization and Embryo Implantation I. ImplantationintheHumanasViewedbyCanonLaw, CivilLaw,andNaturalReason 3 HOWARDW. JONES, JR. , RICHARDA. MCCORMICK, AND SUSAN L. CROCKIN 2. TheImpactofMaternalAgeandOvarianAge onImplantationEfficiency...12 STEVEN SPANDORFER AND ZEV ROSENWAKS Part II. CellularAspects ofImplantation 3. VascularInvasionDuringImplantationandPlacentation 23 ALLEN C. ENDERS AND THOMASN. BLANKENSHIP 4. OxygenRegulatesHumanCytotrophoblastProliferation, Differentiation,andInvasion:Implicationsfor EndovascularInvasioninNormalPregnancy andPreeclampsia 39 OLGA GENBACEV,YAN ZHOU, MICHAEL T. McMASTER, JOHNW. LUDLOW, CAROLINEH. DAMSKY, AND SUSAN1. FISHER 5. Embryo-MaternalInteractionsafterDiapause inaMarsupial 54 MARILYNB. RENFREE AND GEOFFREY SHAW IX x Contents 6. CellularInteractionsandtheCysteineProteinases intheProcessofMouseImplantation 67 BRUCE BABIARZ, SUZANNE AFONSO, ANDLINDA ROMAGNANO Part III. HormonalRegulation 7. NovelSteroid-RegulatedMarkersofImplantation 83 INDRANIC. BAGCHI 8. MolecularSignalinginImplantation 92 SANJOYK. DAS, BIBHASHC. PARIA, AND SUDHANSU K. DEY 9. IdentificationofProgesterone-RegulatedGenes intheUterus 107 CINDEER. FUNK, BERTW. O'MALLEY, AND FRANCESCO1. DEMAYO PartIV. MolecularMarkersofReceptivity 10. MucinsProvideaBarriertoEmbryoImplantation 123 MARYM. DESOUZA, GULNARA. SURVEYOR, XINHUI ZHOU, JoANNE JULIAN, ANDDANIELD. CARSON II. PotentialInvolvementofTrophinin,Bystin, andTastininEmbryoImplantation 132 MICHIKON. FUKUDA, DAITA NADANO,NAO SUZUKJ, AND JUN NAKAYAMA 12. OsteopontininHumanEndometrium: ARoleinEndometrialReceptivityand EmbryoImplantation? 141 CHRISTOS COUTIFARJS,AKINYINKA OMIGBODUN, PIOTR ZIOLKIEWICZ, AND JOHN HOYER PartV. TrophoblastFactors 13. TheRabbitasaModelforImplantation: InVivoandInVitroStudies 151 LORENH. HOFFMAN,D. RACHEL BREINAN, AND GARETHL. BLAEUER 14. RegulationofTrophoblastEndocrineFunction: ThePlacentaDoesItsOwnThingTranscriptionally...161 JEROMEF. STRAUSSIII ANDLEE-CHUANKAo Contents XI 15. TranscriptionFactorsRegulatingtheDifferentiation oftheTrophoblastCellLineage 167 IANC. SCOTTANDJAMESC.

Growth Hormone is a fitting addition to the Endocrine Updates Series. The aim of these publications is to provide the clinician with cutting-edge, yet succinct, access to the latest advances in endocrinology. Current interest in this rapidly evolving area of endocrinology makes this a timely and important update. Growth Hormone joins Dr. Fagin's Thyroid Cancer in continuing the standard of excellence as the fourth volume in this series of topical updates. Shlomo Melmed, MD, Series Editor, Endocrine Updates Ten years ago, many endocrinologists were still skeptical that growth hormone (GH) played an active role in adult metabolism. This is, perhaps, surprising given that GH deficiency (GHD) in adulthood had been `recognized' as long ago as the 1960s. During the last ten years studies have shown that GHD in adulthood is a far-reaching syndrome associated with abnormal body composition, reduced bone mineral density with an increased fracture rate, increased cardiovascular morbidity and impaired cardiac function, as well as reduced exercise performance and decreased psychological well-being. Importantly, it is also clear, from placebo-controlled trials, that GH replacement therapy can normalize body composition, increase bone mineral content and improve the cardiovascular risk factor profile. GH replacement therapy also improves cardiac performance and exercise capacity, increases muscle strength and improves well-being and quality of life. The aim of Growth Hormone is to provide a critical update of current knowledge about adult GHD and the future role of GH/IGF-1 in adult medicine. For this purpose, contributions from a number of research groups have been invited. It is my hope that the book may not only serve as an introduction to the field, but also stimulate further research within this exciting area.

The Seventh International Congress of Mucosal Immunology held in Prague, the beautiful old capital of The Czech Republic, 16-20 August 1992, was the first to be sponsored by the Society for Mucosal Immunology, and was the largest since their inception 20 years earlier in Birmingham, Alabama. It was attended by 624 participants who gave 538 presentations, more than 10 times the numbers of the first meeting; these proceedings contain 354 papers that were submitted for publication. The political events in Europe that made it possible to hold this Congress in Prague also allowed for the first time the participation of large numbers of scientists from Eastern Europe, as weil as from Asia, and the organizers were truly gratified by this happy circumstance. It is now clear not only that mucosal immunityencompasses the huge area of mucosal surfaces and most physiological organ systems, but also that mucosal immunology extends over the whole global surface and all continents! The sheer size of the Congress and number of manuscripts unfortunately entailed some unexpected problems in editing and assembling the proceedings, partly due to the diversity of linguistic styles not represented at earlier meetings, and we apologize to the authors who have patiently awaited the publication of their contributions.

This volume will explore the epidemiology and the basic mechanisms of each of these prenatal phenomena, in an attempt to explain the role of the prenatal environment in promoting postnatal weight gain. This information will contribute to resolving the nature-nurture controversy. This information provides guidance to clinical practitioners involved in both prenatal and postnatal care. This volume further stimulates research into underlying mechanisms and prevention and treatment of this phenomenon.

It is an authentic privilege to have the opportunity to assemble and edit a new volume on "Prolactin," the first in several decades to be devoted to this fascinating hormone in all its aspects. The obvious clinical rationale for understanding prolactin (PRL) is the frequent occurrence of prolactinomas, the most common type of pituitary tumor. Fortunately, medical management of prolactinomas can be based on our under standing of the physiology of hypothalamic control of the lactotroph. Armed with this knowledge, therapies for proiactinomas are highly successful and well tolerated. Be cause of the historical and practical importance of knowledge regarding the hypothala mus-Iactotroph axis, the first chapters of this volume are dedicated to reviewing the physiology, development, and cell biology of lactotroph regulation. Chapters focusing on prolactinomas and related clinical issues follow these. PRL is the primary hormone that is responsible for "parental care" in many verte brate species. This reproductive strategy is not unique to mammals, but it has devel oped through evolution to be the central distinguishing feature of the mammalian life cycle. Among the mammals, mice have become the most effective research species in recent years. This can be traced to the development of a wide range of methods for manipulating mouse genetics, and thereby influencing development, physiology and behavior. Mice also provide a profound illustration of the physiological challenges faced in maternity. Female mice undergo a post-partum estrous, and often are both pregnant and lactating simultaneously.

Growth Hormone and the Heart endeavors to bring together knowledge that has been accumulated in the area of GH and the heart, from basic to clinical studies, by research groups working on this topic throughout the world. Lessons from different experimental models and from several human diseases (acromegaly, adult GH deficiency, heart failure) suggest to endocrinologists and cardiologists that GH may not only have a role in the physiology and pathophysiology of heart function, but that GH itself may have a place in the treatment of primary heart diseases (such as dilated cardiomyopathy) or of cardiac complications of hypopituitarism. Growth Hormone and the Heart will be a useful update of the research produced in the field of cardiovascular endocrinology. The Editors also hope that this book will serve as the primary step in the recognition of the wide physiological and clinical significance of GH and heart interactions.

Genetics of Diabetes Mellitus is intended to be a resource for both researchers in the field as well as endocrinologists, diabetologists, and geneticists who seek to learn more about this rapidly changing and important field. The text contains chapters from experts in the area who review aspects of the genetics of both type 1 and 2 diabetes mellitus as well as various syndromic forms of diabetes. The chapters are approachable for those who are not experts in the field of genetics but also comprehensive, so as to serve as an important resource for researchers interested in the genetics of diabetes mellitus. A description of basic concepts of the genetics of complex diseases like type 1 and type 2 diabetes is provided as background. Type 1 diabetes is addressed in chapters exploring genetic determinants that affect the autoimmune process characteristic of type 1 diabetes, the role of the insulin gene in the pathogenesis of type 1 diabetes and additional genes that may impact upon the risk of type 1 diabetes. The impact of genetic determinants on the pathophysiology of type 2 diabetes is covered, as are chapters that address specific genes that are important for the development of type 2 diabetes. Finally, syndromic forms of diabetes, including Maturity Onset Diabetes of the Young and mitochondrial diabetes, and the insight that these disorders provide into more common forms of diabetes are reviewed. Thus, this comprehensive and up-to-date text will serve as an important resource for those actively engaged in research in this area and clinicians treating these patients to provide an up-to-date entree for those seeking to become more knowledgeable in the area.

This volume is a collection of the most significant contributions to the 4th International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE: STRATEGIES OF PREVENTION OF CORONARY HEART DISEASE, CARDIAC F AlLURE, AND STROKE held in Washington, D. C. in April 1997. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological, clinical, and biological evidence that individuals from industrialized countries often possess two or more risk factors which synergistically increase the global risk profile. This has become more evident in recent years with the increase in life expectancy of populations in the industrialized countries. The evidence that a combination of risk factors confers a very high risk of developing cardiovascular diseases, is of pivotal interest in the process of detection of patients who will benefit the most from pharmacological treatment. Many recent epidemiological data identifying the intrinsic and environmental factors contributing to the development of atherosclerosis are discussed. These results, in parallel with basic and clinical research, underline atherosclerosis as a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure rheologic forces, carbohydrate tolerance, and thrombogenic factors, including fibrinogen, tissue factor, PAl-I, and homocysteine. Furthennore, the risk associated with anyone of these risk factors varies widely depending on the level of the associated atherogenic risk factors. Hyper cholesterolemia and hypertriglyceridemia, for instance, are more common than would be expected by chance among hypertensive patients.

Diabetes and cardiovascular disease together account for the largest portion of health care spending compared to all other diseases in Western society. This work seeks to provide an understanding of the causes of diabetes and its cardiovascular complications. As this understanding becomes more widely appreciated, it will serve as a foundation for evidence-based care and wider acceptance of sound science. The International Conference on Diabetes and Cardiovascular Disease, held in Winnipeg, in June 1999, was organized to bring together a multi-disciplinary group of researchers dedicated to further knowledge amongst researchers, care givers, and the managers of the health system. The invited speakers submitted their works for publication, which serves as the basis for this book. Major themes include: epidemiology of diabetes mellitus, metabolic risk factors in diabetes and cardiovascular disease, hypertension in diabetes mellitus, cardiac function in diabetes, glycemic control and improved cardiovascular function, diabetes management, and endothelial function in diabetes.

The evolution ofdata about the HIV-Associated Lipodystrophy Syndrome has been rapid. The syndrome itself is complex and controversial. Although great progress has been made in understanding epidemiology and etiology of the syndrome, much about the syndrome remains mysterious. It was our intention to assist HIV providers with a framework for understanding the status and complexities ofthe field. Each author was requested to provide an evidence-based discussion of a topic for which they have expertise. While it is impossible that such a volume be completely comprehensive, we believe that the approach of this book will allow the reader to develop a relatively complete snapshot of the syndrome. We also believe that the reader of this volume will be able to confront the emerging literature on the HIV-associated lipodystrophy syndrome with a critical eye and that the volume will provide a context in which to place additional data as they are published.

Despite the advent of insulin for clinical use in 1922, our ability to control hypergly cemia and prevent the long term sequelae ofthe disease remains limited. Thus normalization of the milieu interieur with physiologic responses of insulin and metabolites remains an elusive but critically important goal. The developing endocrine pancreas provides a model system that speaks to many challenges of the transplantation biologist. Thus the attempt to of vascularization, growth and development, immunologic toler recapitulate the ontogeny ance, and glucose responsive insulin secretory capacity of fetal islet tissue provides a tantalizing possibility to replace insulin secreting tissue in persons with diabetes. Studies of this tissue are also important because of the implications such investigations have for genetic and molecular biological approaches to restoring insulin secretion as well as for providing clues to enhancing the growth and repair of islets that have been the target of autoimmune disease. Investigators in the area offetal islet transplantation comprise a small group scattered throughout the world scientific community. Therefore it seemed important to provide a forum where these scientists could gather, share ideas, and achieve consensus such that progress in this rapidly evolving area could be facilitated. The conference would have remained a dream if the support of the Okla Basil Meade, Jr. family had not made it manifest."

Aaron I. Vinik, M.D., Ph.D. I IEastem Virginia Medical School The Diabetes Institutes Norfolk, Virginia 23510 This symposium, held in June 1991, was a gathering of international scientists to exchange their views on current concepts of cell growth and differentiation. Each scientist was asked to present a topic of their research related to cell growth and regeneration and to participate in a round table conference elaborating on current knowledge and sharing their experiences. By furthering this promising area of endeavor, a means of understanding ontogeny of cell development and of providing insights into tumor biology would prevail. Of prime importance was the anticipation that new information from a better understanding of the normal evolution of the pancreatic islet would generate alternative approaches to curing diabetes. This forward serves as a short introduction to the concept of pancreatic islet regeneration and the models currently in use to study the process. DEVELOPMENTAL ORIGIN OF ISLETS DURING EMRYOGENESIS The developing pancreas appears as a protrusion from the dorsal surface of the l embryonic gut. The different islet cell types appear sequentially during development in vivo. It therefore seems reasonable to propose that coordinated growth is dependent upon specificity of growth factors.

Diabetes mellitus is rapidly increasing in prevalence throughout both developed and developing countries. The social and economic burden of this disease is estimated to cost 14 billion dollars worldwide. In the USA alone, 15 million individuals are diabetic, nearly half of them unaware of their condition. Complications of diabetes mellitus are the leading causes for blindness, limb amputation and chronic renal failure and kidney transplantation in industrialized countries. Further, diabetes mellitus per se and the metabolic derangement associated with diabetes are important risk factors for cardiovascular disease. Diabetes, as defined by an elevated fasting blood glucose level is presently subdivided in etiologically distinct groups. The most prevalent being type 2 (adult onset) diabetes characterized by insulin resistance and failure of the ~-cell to supply insulin in amounts sufficient to meet the body's needs. Type 1 (juvenile) diabetes, most commonly with an onset during childhood and adolescence, is caused by an auto-immune destruction of the pancreatic ~-cells. The causations of both type 1 and type 2 diabetes involve a combination of complex genetic traits and environmental influences. A third category are the mature onset diabetes of the young (MODY). This comparatively small group of patients (-10% of diabetes) presents relative early in life "30 years of age) compared to the more common late onset type 2 diabetes.

The aim of this symposium was to provide basic and clinical investigators with the latest information on the biology of wound healing and tissue repair. Written and edited by eminent experts in the field, the papers cover the general concepts of wound healing; the role of nutrients; endogenous growth factors; clinical applications of growth hormone and IGF-1 therapy; and clinical applications of peptide growth factors.

Following 50 years of glucocorticoid use in a clinical setting, an international body of expert scientists and physicians presents the most expansive survey of glucocorticoid pharmacology to date. This work traces the history of glucocorticoid biology from the seminal description of glucocorticoid insufficiency by Thomas Addison in the mid-19th century, up to current advances in elucidating the molecular basis of glucocorticoid action. Important discoveries are presented, as well as milestones in drug development, a survey of current clinical practice, and prospects for novel glucocorticoid-based therapeutics. Scientists and clinicians will appreciate the scope of this work, which is of special interest to workers in the fields of endocrinology, inflammation and autoimmune disease.

Montreal has had a longstanding interest in somatostatin. Two years ago when the final planning began for the International Con gress of Endocrinology in Quebec City in July 1984, we seized the op portunity for having a separate Satellite Symposium on somatostatin here in Montreal. We felt that after a decade of uniformly vigorous growth in somatostatin research, the opportune moment had arrived for a review of the most significant past developments and for setting the directions for the future. Knowing the futility of trying to cover every aspect of the burgeoning somatostatin field in a two day scientific program, we opted for a detailed analysis of selected areas which were reasonably mature and of areas of greatest new activity. To attain these objectives, 27 leading international experts actively involved in their fields were invited to present an indepth review of their work in one of five major categories of somatostatin research. Thirty minutes at the end of each session were assigned for a three way, comprehensive discussion of some of the core concepts between the session moderators, the panellists and the audience. The feedback that we have received from the particip ants leaves little doubt that the meeting was a scientific and social success. This book fulfills our final commitment towards the Meeting which was to record the proceedings in a timely publication.

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.

Inhibin, activin, and follistatin were originally discovered as hormonal fac- tors a decade ago. Subsequent studies revealed that they are widely distrib- uted anatomically and have multiple biological functions in a wide range of cells and tissues. Since the last Symposium three years ago, there has been remarkable progress toward defining activin's roles in controlling hormone secretion, cell differentiation and proliferation, mesoderm induction in em- bryos, nerve cell survival, and promotion of bone growth. Furthermore, the characterization of activin receptors as serine and threonine kinases and the identification of intracellular mediators such as the Smads have provided key elements for the eventual understanding of signaling mechanisms for activin and the other members of the TGF-beta superfamily. The unknown in this integrative field, however, remains far greater than the known. For ex- ample, we are just beginning to exploit the recently improved activin, inhibin, and follistatin two-site assays for the evaluation of the physiological and pathophysiological functions of these proteins. Also, we have only a rudi- mentary understanding of the mechanisms by which inhibin blocks activin, and many steps in the pathways linking the formation of ligand-receptor(s) complexes to transcriptional regulation are unclear. The aim of the Third Symposium was to bring together scientists from diverse fields to share technical and conceptual developments. The program was framed with the intention to include a wide range of timely research topics.

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.

In September of 1977 scientists from many countries met at the Asticou Inn in Maine to present and discuss papers written especially for this monograph. The presentations were informal and directed to the special interests of the audience in order to generate discussions. The authors, many of whom are pioneers and leaders in their field, then had the oppor tunity to revise their contributions, which were brought together with the edited discussions to form this volume. The basic research studies presented here are important because of the essential role of gonadotropins in regulating the ovary and testis. This monograph will therefore be of interest to those concerned with fertility regulation, population control, possible new methods for contraception, and to those concerned with reproduction in domestic animals. Re searchers in other fields may find this monograph useful, as it has been de termined that gonadotropins are secreted by many tumors and are im plicated in many cancers. Human choriogonadotropin also seems to be found in most, if not all, cells of the human body. The significance of this, however, is unknown."

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.

Calcium-Sensing Receptor provides an overview of various aspects of the calcium receptor's biochemistry, physiology and pathophysiology that is suitable both for those who have been working in the field of Ca2+0-sensing as well as those who are new to this discipline. Calcium-Sensing Receptor is the nineteenth volume published in the Endocrine Updates book series under the Series Editorship of Shlomo Melmed, MD.