Acth Action In The Adrenal Cortex From Molecular Biology To Pathophysiology

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.

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.

Stress has been recognized as an important factor in the development or recurrence of various mental disorders, from major depressive disorder to bipolar disorder to anxiety disorders. Stressful stimuli also appear to exert their effects by acting upon individuals with susceptible genotypes. Over the past 50 years, animal models have been developed to study these dynamic interactions between stressful stimuli and genetically susceptible individuals during prenatal and postnatal development and into adulthood. Stress and Mental Disorders: Insights from Animal Models begins with a discussion of the history of psychiatric diagnosis and the recent goal of moving toward precision psychiatry, followed by a review of clinical research on connections between stressful stimuli and the development of psychiatric disorders. Chapters are also included on neuroendocrine, immune, and brain systems involved in responses to stress. Additional chapters focus on the development of animal models in psychiatry and the susceptibility of the developing organism to stressful stimuli. Subsequent chapters are devoted to animal models of specific stress-sensitive psychiatric disorders, including schizophrenia, autism spectrum disorders, bipolar disorder, anxiety disorders, depression, and post-traumatic stress disorder. These chapters also focus on identification of promising molecular targets for development of new drug therapies. The section concludes with a chapter on animal models of resilience to stress-induced behavioral alterations as a newer approach to understanding why some animals are susceptible to stress and others are resilient, even though they are essentially genetically identical. The final chapter discusses how these basic laboratory studies are providing promising leads for future breakthroughs in the diagnosis, treatment, and prevention of mental disorders.

Genetic Diagnosis of Endocrine Disorders, Second Edition provides users with a comprehensive reference that is organized by endocrine grouping (i.e., thyroid, pancreas, parathyroid, pituitary, adrenal, and reproductive and bone), discussing the genetic and molecular basis for the diagnosis of various disorders. The book emphasizes the practical nature of diagnosing a disease, including which tests should be done for the diagnosis of diabetes mellitus in adults and children, which genes should be evaluated for subjects with congenital hypothyroidism, which genetic tests should be ordered in obese patients or for those with parathyroid carcinoma, and the rationale behind testing for multiple endocrine neoplasias. Offers a clear presentations of pharmacogenetics and the actual assays used in detecting endocrine diseases Teaches the essentials of the genetic basis of disease in each major endocrine organ system Offers expert advice from genetic counselors on how to use genetic information in counseling patients Includes new chapters on the genetics of lipid disorders and glycogen storage diseases, genetics of hypoglycemia, and whole genome/exome sequencing

Anxiety affects millions, manifesting as generalized anxiety disorder (GAD), obsessive compulsive disorder, panic disorder, phobias, post-traumatic-stress disorder (PTSD), and social anxiety disorder. Not only are anxiety disorders common, but they are also crippling, frequently co-occurring and predict high risk for depressive disorders. Shared mechanisms may explain the overlapping features of many anxiety disorders and account for associations with other highly-impairing conditions, such as major depression and substance use. Beyond risk for specific disorders, anxiety also predicts a number of other adverse outcomes, including suicidal behavior, medical problems, social, and economic difficulties. Conversely, disorder-specific mechanisms may also exist and explain the unique features of each syndrome. Thus, it is important to understand both shared and specific aspects of anxiety. The Primer on Anxiety Disorders provides early-stage practitioners and trainees, as well as seasoned clinicians and researchers, with need-to-know knowledge on diagnosis and treatment. Clinical cases are used throughout the book to enhance understanding of and illustrate specific disorders, comorbid conditions and clinical issues. To facilitate an integrative approach, content allows clinicians to understand patient characteristics and tailor interventions. The integrated approach of each chapter includes recent research on genetics and neuroscience to understand the mechanisms of anxiety disorders, focusing on the forthcoming new nosology in DSM-5. Chapters further integrate innovative advances in clinical research providing research on a range of discoveries regarding biomarkers of illness, biological predictors of treatments and the effect of treatment on neurocircuitry.

This volume provides comprehensive coverage of the current knowledge of the physiology of the endocrine system and hormone synthesis and release, transport, and action at the molecular and cellular levels. It presents essential as well as in-depth information of value to both medical students and specialists in Endocrinology, Gynecology, Pediatrics, and Internal Medicine. Although it is well established that the endocrine system regulates essential functions involved in growth, reproduction, and homeostasis, it is increasingly being recognized that this complex regulatory system comprises not only hormones secreted by the classic endocrine glands but also hormones and regulatory factors produced by many organs, and involves extensive crosstalk with the neural and immune system. At the same time, our knowledge of the molecular basis of hormone action has greatly improved. Understanding this complexity of endocrine physiology is crucial to prevent endocrine disorders, to improve the sensitivity of our diagnostic tools, and to provide the rationale for pharmacological, immunological, or genetic interventions. It is such understanding that this book is designed to foster.