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Receptors and Gene Expression It is now more than three years since the last Meadow Brook Conference on Hormones, and a great deal has happened in the meantime. We have become comfortable with the totally unanticipated fact that the coding sequences of genes are in discontinuous arrangements and that the RNA transcribed from them must be extensively processed to form messenger RNA. We have also learned about the strategy of "mixing and matching" of genetic segments so that a small amount of DNA can go a long way in producing a huge variety of different proteins, as in the immunoglobulin system. The explosive effort directed toward DNA sequence analysis has led us to the conclusion that there are signals within the DNA that specify sites of transcription initiation and possibly sites for interacting with regulatory molecules such as hor mones and their receptors. The current intense interest in the structure of chromatin beyond the nucleosome-that is, the superstructural characteris tics of the genetic material-is finally yielding meaningful results that give promise for understanding the regulation of gene activity. ROBERT F. GOLDBERGER Preface Research on the molecular mechanism of steroid hormone action continues at an extraordinary pace and a great deal of progress has been made. Steroid hormones have been localized on target genes providing the long awaited evidence for the concept of a direct effect of the steroid-receptor complex on gene regulation. Purified steroid receptors have been dissected to identify different functional domains.
Within the last two decades endocrinological research has taken a definite tum toward biochemistry and molecular biology. This has resulted in a new discipline called' 'molecular endocrinology. " Studies on the mechanism of hormone action have continued to make headlines with fundamental discov eries in receptor action and gene regulation. Recently the insect endocrino logists have also begun to explore the molecular mechanism of steroid hor mone action taking advantage of the vast number of Drosophila mutants, the library of Drosophila gene, and several well-characterized cell-lines. The availability ofthe recombinant DNA technology has provided a truly revolu tionary tool in the hands of the molecular endocrinologists. "Gene Regula tion by Steroid Hormones" is compiled and presented in this frontier spirit, and we hope that this volume will serve not only the active investigators in the field but will also be very useful to students and researchers with a gen eral interest in regulatory biology. The book is an offshoot of the Conference on Molecular Mechanism of Steroid Hormone Action held at the Meadow Brook Mansion of Oakland University in the fall of 1978. We wish to acknowledge the financial assist ance from the National Science Foundation and Oakland University. The conferees will never forget the warmest hospitality of Dr. LOWELL EKLUND and his staff at the Meadow Brook center and we also wish to express per sonal gratitude to many of our students and colleagues for helping us to make the conference a great success.
This updated second edition of Diagnosis and Management of Ovarian Disorders provides thorough, yet succinct insight into the ever-changing realm of ovarian disorders. It presents a novel multidisciplinary approach to the subject as described by clinicians, surgeons, pathologists, basic scientists and related medical researchers. Topics covered include reproductive technology, early diagnosis of ovarian cancer, and management of menopause among others. The breadth of information provided by this book will appeal to clinicians and researchers involved in the study and treatment of ovarian disorders.KEY FEATURES* Includes updated information on early diagnosis of ovarian cancer* Reviews new diagnostic techniques for ovarian disorders* Discusses latest information on reproductive technology* Presents translational treatment linking laboratory research with clinical medicine
Some investigators have hypothesized that estrogens and other hormonally active agents found in the environment might be involved in breast cancer increases and sperm count declines in humans as well as deformities and reproductive problems seen in wildlife. This book looks in detail at the science behind the ominous prospect of "estrogen mimics" threatening health and well-being, from the level of ecosystems and populations to individual people and animals. The committee identifies research needs and offers specific recommendations to decision-makers. This authoritative volume: Critically evaluates the literature on hormonally active agents in the environment and identifies known and suspected toxicologic mechanisms and effects of fish, wildlife, and humans. Examines whether and how exposure to hormonally active agents occursâ€"in diet, in pharmaceuticals, from industrial releases into the environmentâ€"and why the debate centers on estrogens. Identifies significant uncertainties, limitations of knowledge, and weaknesses in the scientific literature. The book presents a wealth of information and investigates a wide range of examples across the spectrum of life that might be related to these agents.
The first Meadowbrook Symposium was held in 1978 and during the intervening ten years our knowledge concerning how steroid hormones function at the level of gene expression has advanced by leaps and bounds. In this volume, which sum marizes our fourth meeting, these advances are very evident. What seemed like science fiction ten years ago has become commonplace science. Who would have imagined that we could synthesize a nucleotide sequence that binds a specific steroid receptor and acts as a controlling element for gene expression? No one; but as is evident from the results reported in several chapters, this technique is yielding a wealth of information. Using these and other techniques it has become apparent that gene transcription is controlled by interactions between transacting factors and DNA recognition sequences (response elements). These transacting factors appear to be members of a large gene family that includes steroid hormone receptors, transcription factors, protooncogenes and homeobox proteins. Thus a great deal has been learned, but as usual, questions remain. Many of these questions are posed by the findings and observations found in several chapters in this volume. Non hormone binding forms of steroid receptors and their relevance to receptor down regulation, recycling and biological response remain a mystery. The quantitative relationship between receptor binding and biological response still presents agonizing problems. These and many other intriguing questions are discussed in this volume and set the stage for what should be a most rewarding time in endocrinology. Winter 1989 ARUN K.
Over the past few years there have been considerable advances in our understanding of cellular control mechanisms, and current research is now linking areas of biology that were previously thought of as being quite separate. Molecular Aspects of Cellular Regulation is a series of occasional books on multidisciplinary topics which illustrate general principles of cellular regulation. Previous volumes described Recently Discovered Systems of Enzyme Regulation by Reversible Phosphorylation (Volumes 1 and 3), The Molecular Actions of Toxins and Viruses (Volume 2), Molecular Mechanisms of Transmembrane Signalling (Volume 4) and Calmodulin (Volume 5). This sixth volume, The Hormonal Control of Gene Transcription, has now been published to highlight recent important advances in our understanding of this topic which is linking two of the most active areas of current biochemical and molecular biological research (hormone action and gene transcription) and leading to the emergence of unifying concepts.
The field of steroid hormone action has continued to expand into the realm of molecular biology at a pace even faster than most of us ever imagined. techniques of molecular biology have made it possible to clone The hormone-regulated genes and to examine steroid-receptor interactions with these genes. Nucleotide sequences of these genes, which show preferential binding of steroid receptors, have been identified. These results are complemented by the identification of chromatin acceptor proteins, which also show preferential binding for steroid-receptor complexes. Thus, one can envision the day when cloned genes, purified acceptor proteins, and receptor-steroid complexes will be recombined in vitro to form a functional unit. Cellular localization of steroid receptors has undergone recent revision, and it now appears that receptors are localized primarily in the nuclear compartment. These findings, although controversial, will lead to a reassessment of many of the previous concepts of steroid-receptor interactions and regulation. The way in which these observations at the of physiology, molecular and cellular levels fit into the overall scheme development, and evolution are continuing to progress, and the future promises some very exciting syntheses of understanding at all levels of biological organization. The third Meadow Brook Conference on hormones was held in order to bring together investigators who will undoubtedly contribute heavily to this future synthesis and to permit a free exchange of ideas and concepts as they relate to the current state-of-the-art in molecular endocrinology. Spring 1986 ARUN K. Roy JAMES H. CLARK Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The Intemational Meeting on Vitamin B6 and Carbonyl Catalysis took place on Capri, Italy from 22nd to 27th May 1994 and was organized in conjunction with the 3rd Symposium on PQQ and Quinoproteins. It was an extraordinary occasion for scientists from all over the world to meet and discuss new developments in these overlapping fields. Several sessions were dedicated to the molecular aspects of Vitamin B6 and Quinone dependent enzymes, as well as to the cellular, biomedical and nutritional aspects. The congress was inaugurated by Paolo Fasella in his capacity as General Director of Science, Research and Development of the Commission of the European Communities, with an overview on Intemational Scientific Collaboration. The scientific sessions started with a talk on the History of Vitamin B6 given by David Metzler who at the very last minute presented Esmond Snell's paper adding some personal remarks. Unfortunately, both Esmond Snell and Alton Meister had to unexpectedly cancel the trip to Capri. These proceedings contain the papers presented as oral contributions and a few selected poster presentations. The limited number of pages meant we could not publish many interesting poster presentations, including those selected for the three lively and exciting evening poster discussion sessions called by the organizers "Vino, taralli and ... discussion".
This volume provides a detailed overview of the mechanisms by which steroid hormones regulate gene activity in target cells. It should be of interest to molecular biologists, endocrinologists, pharmacologists and clinicians interested in gene regulation hormones and steroid antagonists.
From the tissue culture dish to genetically modified mice, this volume explores the long recognized role of steroid hormones in regulating cell proliferation and differentiation. Many striking effects of steroid hormones are apparent during development and neoplasia and these topics are covered extensively. Several chapters address the pharmacological uses of steroid and related hormones, their analogs and antagonists in controlling growth of endocrine cancers. This book also highlights the complex role of cross talk between steroid hormones and signals initiated at the cell surface in the regulation of cell cycle in hormone responsive tissues.