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Glucocorticoids regulate multiple metabolic and developmental processes and play a vital role in the maintenance of basal and stress-related homeostasis. For the last 50 years, pharmacologic doses of glucocorticoids have been used in the treatment of inflammatory, autoimmune, and lymphoproliferative diseases and in the prevention of allograft rejection, while substitution doses have been employed in the management of adrenocortical insufficiency. aspects of glucocorticoid action, in particular, (i) the impact of maternal and early life stress on stress-related gene regulation in the offspring; (ii) the importance of glucocorticoids and their receptors; (iii) further understanding of the mechanisms of GR action, including its effect on chromatin modulation, its interaction with coactivators and corepressors, and the genetic dissection of GR function in mice; (iv) The interaction of hGR with other transcription factors, such as NF-kappa-B, p53, transforming growth factor beta (TGF-beta) and the chicken ovalbumin upstream promoter transcription factor II (COUP-TFII); recycling, ubiquitination and degradation of the receptor, actions of the GR-beta isoform, a novel synthetic nonsteroidal target gene-specific agonist, the importance of target tissue activity of 11-beta-hydroxysteroid dehydrogenase type 1 in glucocorticoid action in health and disease, the interaction of the receptor with the nutrient carnitine, the anthrax products protective antigen (PA) and lethal factor (LF), and the human immunodeficiency virus type-1 (HIV-1)-encoded molecules Vpr and Tat; (vi) an update on the effects of glucocorticoids on the immune system; and (vii) the clinical implications of glucocorticoid action, including glucocorticoid resistance/hypersensitivity, familial and sporadic glucocorticoid resistance, and the effects of stress and depression.
This timely volume provides a comprehensive overview of glucocorticoids and their role in regulating many aspects of physiology and their use in the treatment of disease. The book is broken into four sections that begin by giving a general introduction to glucocorticoids and a brief history of the field. The second section will discuss the effects of glucocorticoids on metabolism, while the third section will cover the effects of glucocorticoids on key tissues. The final section will discuss general topics, such as animal models in glucocorticoid research and clinical implications of glucocorticoid research. Featuring chapters from leaders in the field, this volume will be of interest to both researchers and clinicians.
Osteoporosis is one of the most clinically relevant disabling chronic disease encountered in clinical practice. A common cause of osteoporosis is glucocorticoid excess, as glucocorticoids may increase bone resorption, inhibit bone formation, have indirect actions on bone by decreasing intestinal calcium absorption and induce hypercalciuria. This book presents a comprehensive overview of the effects of glucocorticoids on bone metabolism and structure and on the diagnosis and treatment of glucocorticoid-induced osteoporosis. It aims at providing updated information on the pathogenesis, diagnosis and treatment of this often dramatic complication of glucocorticoid excess. Being one of the few publications completely devoted to glucocorticoid-induced osteoporosis it will heighten the awareness of specialists who prescribe glucocorticoids of the clinical relevance of this treatment complication. 'Glucocorticoid-Induced Osteoporosis' is addressed to clinical experts as well as to general practitioners who will both benefit from the comprehensive and integrative view of the management of patients exposed to glucocorticoids.
The hypothalamic-pituitary-adrenal axis controls reactions to stress and regulates various body processes such as digestion, the immune system, mood and sexuality, and energy usage. This volume focuses on the role it plays in the immune system and provides substantive experimental and clinical data to support current understanding in the field, and potential applications of this knowledge in the treatment of disease. - Evidence presented in this book suggests that the nervous, endocrine, and immune systems form the Neuroendoimmune Supersystem, which integrates all the biological functions of higher organisms both in health and disease for their entire life cycle - Contributors include both the scientists who initiated the work on the HPA axis and on the autonomic nervous system, and those who joined the field later
Nuclear Receptors in Development and Disease, Volume 125, the latest volume in the Current Topics in Developmental Biology series, covers nuclear receptors in development and disease, and includes contributions from an international board of authors. New chapters in this release cover the Evolution of Nuclear Receptors and Ligand Signaling: Towards a Soft Key–Lock Model?, The Function and Evolution of Nuclear Receptors in Insect Embryonic Development, Nuclear Receptors in Skeletal Homeostasis, Estrogen Hormone Biology, and the Mechanisms of Glucocorticoid Action During Development. The book's chapters provide a comprehensive set of reviews that cover such topics as nuclear differentiation and remodeling, evolution of receptors, ligand signaling and neural development. - Covers the area of nuclear receptors in development and disease - Includes contributions from an International board of authors - Provides a comprehensive set of reviews on topics as nuclear differentiation and remodeling, evolution of receptors, ligand signaling and neural developments
Mifepristone (RU486), the first clinically available antiprogestin, has generated great interest since its discovery in the early 1980s. Today, it is recognized that mifepristone, along with other antiprogestins, has a potentially significant therapeutic role in human health and disease, with likely applicability to a variety of pregnancy-related conditions (e.g., management of labor) and to contraception, endometriosis, and cancer, among others. But because mifepristone has been studied and used most widely as a means of nonsurgical abortion, political issues have thus far limited research on the drug and prevented its introduction into the U.S. market. This book provides an unbiased evaluation of current knowledge about both the fundamental nature of antiprogestins as well as their possible use in treating numerous diseases and conditions, and it contains recommendations for future research.
Developmental programming is a rapidly advancing discipline of great importance to basic scientists and health professionals alike. This text integrates, for the first time, contributions from world experts to explore the role of the placenta in developmental programming. The book considers the materno-fetal supply line, and how perturbations of placental development impact on its functional capacity. Chapters examine ways in which environmental, immunological and vascular insults regulate expression of conventional and imprinted genes, along with their impact on placental shape and size, transport, metabolism and endocrine function. Research in animal models is integrated with human clinical and epidemiological data, and questions for future research are identified. Transcripts of discussions between the authors allow readers to engage with controversial issues. Essential reading for researchers in placental biology and developmental programming, as well as specialists and trainees in the wider field of reproductive medicine.
Core Topics in Endocrinology in Anesthesia and Critical Care provides a comprehensive, practical overview of the perioperative management of patients with endocrine disorders, giving clear diagnostic advice and management guidelines. This book considers the management of patients with endocrine disorders of the pituitary, thyroid, parathyroid and adrenal glands, including rarer disorders such as MEN syndrome. It then considers all aspects of the perioperative management of diabetic patients, including paediatric, obstetric and ambulatory patients. Finally it discusses endocrine disorders in the critically ill patient, covering such issues as the topical conundrum of glucose control and the management of diabetic metabolic acidosis, thyroid storm and myxoedema coma. Every chapter reviews the relevant anatomy and pathophysiology and the latest developments in defining the genetic causes are also considered where appropriate. Core Topics in Endocrinology in Anesthesia and Critical Care is an invaluable tool for all anaesthetists and intensivists in their daily clinical practice.
A comprehensive overview of the current research on inflammation and immunopharmacology, with particular attention to the use of anti-inflammatory drugs, this book discusses future trends in this area of pharmacological research. It addresses an audience with basic knowledge in the inflammatory process, immune system and pharmacology. The book meets the needs of graduate students, junior and senior researchers and is useful as a source of the most current information for those already working in these fields.
By stimulating adrenal gland and corticosteroid synthesis, the adrenocorticotropic hormone (ACTH) plays a central role in response to stress. In this Research Topic, a particular attention has been given to the recent developments on adrenocortical zonation; the growth-promoting activities of ACTH; the various steps involved in acute and chronic regulation of steroid secretion by ACTH, including the effect of ACTH on circadian rhythms of glucocorticoid secretion. The Research Topic also reviews progress and challenges surrounding the properties of ACTH binding to the MC2 receptor (MC2R), including the importance of melanocortin-2 receptor accessory protein (MRAP) in MC2R expression and function, the various intracellular signaling cascades, which involve not only protein kinase A, the key mediator of ACTH action, but also phosphatases, phosphodiesterases, ion channels and the cytoskeleton. The importance of the proteins involved in the cell detoxification is also considered, in particular the effect that ACTH has on protection against reactive oxygen species generated during steroidogenesis. The impact of the cellular microenvironment, including local production of ACTH is discussed, both as an important factor in the maintenance of homeostasis, but also in pathological situations, such as severe inflammation. Finally, the Research Topic reviews the role that the pituitary-adrenal axis may have in the development of metabolic disorders. In addition to mutations or alterations of expression of genes encoding components of the steroidogenesis and signaling pathways, chronic stress and sleep disturbance are both associated with hyperactivity of the adrenal gland. A resulting effect is increased glucocorticoid secretion inducing food intake and weight gain, which, in turn, leads to insulin and leptin resistance. These aspects are described in detail in this Research Topic by key investigators in the field. Many of the aspects addressed in this Research Topic still represent a stimulus for future studies, their outcome aimed at providing evidence of the central position occupied by the adrenal cortex in many metabolic functions when its homeostasis is disrupted. An in-depth investigation of the mechanisms underlying these pathways will be invaluable in developing new therapeutic tools and strategies.