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.

In Adrenal Disorders, a panel of distinguished physicians and researchers select the most relevant new findings and integrate them into the existing body of clinical knowledge on adrenal pathologies. The book includes important reviews of disturbances in cortisol homeostasis, and new concepts regarding adrenal tumors and hereditary adrenal diseases. Also discussed are mineralocorticoids and the syndromes of mineralocortoid excess and aldosterone synthase deficiency. Authoritative and insightful, Adrenal Disorders provides physicians and scientists with a comprehensive, state-of-the-art practical guide to the devastating diseases of the adrenals that are so often difficult to diagnose and treat.

This practical resource provides the latest evidence, management strategies and recommendations for the treatment of disorders of the adrenal glands, including related physiology, genetics and pharmacology. This book is divided into three thematic sections. The first covers adrenal physiology, presenting adrenal zonation and development, the regulation of steroidogenesis, and the pharmacology of glucocortisoids. Part two discusses the genetics and pathophysiology of a number of adrenal disorders, including autoimmune Addison’s disease, congenital adrenal hyperplasia, primary aldosteronism, adrenocortical tumors and hyperplasias, and pheochromocytomas and paragangliomas. The final section presents the latest diagnostic and management strategies for these disorders, addressing adrenal insufficiency, adrenal Cushing’s Syndrome and aldosteronism, among others. Over the past twenty years, our understanding of disorders of the adrenal glands has been altered and deepened. Providing a much-needed update to the literature, Adrenal Disorders: Physiology, Pathophysiology and Treatment will be an important resource for both academic and clinical endocrinologists working with the adrenal glands and managing patients with adrenal disorders.

Written by experts and specialized investigators, this book presents a detailed overview of the recent progress in our understanding of the adrenal cortex and its pivotal roles in homeostasis. Genes, molecules and cell compartments directly or indirectly involved in the complex steroidogenesis pathway as well as the resulting end-hormones glucocorticoids, mineralocorticoids and androgens are analyzed. Furthermore, the defects of the genes responsible both for common and rare adrenal disorders are presented. The interactions of the adrenal cortices with the adrenal medulla and their importance in the integration of adrenocortical and adrenomedullary function are discussed. The complex molecular pathophysiology of congenital adrenal hyperplasia is presented; long-term effects of the disorder and the still controversial antenatal therapy are examined. Finally, expert review chapters discuss autoimmune Addison disease and the adrenoleukodystrophy/adrenomyeloneuropathy syndrome.Presenting novel research findings in adrenal gland physiology and pathophysiology, this book is a useful tool not only for pediatric endocrinologists, but also for clinicians and researchers studying human development, organogenesis, mitochondrial biology, nuclear receptors, stress biology and pharmacology.

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

Substantial further advances in our understanding of adrenal development, steroid biosynthesis and adrenocortical disorders necessitate another look at this small but complex organ. In this volume, leaders in the fields of adrenal development, biochemistry and genetics review the most recent findings from bench and bedside research. New aspects of adrenal development and zonation and the novel 'backdoor' pathway to androgen synthesis are discussed. P450 oxidoreductase deficiency (a newly described form of congenital adrenal hyperplasia) and long-term outcome of prenatal treatment of 21-hydroxylase deficiency are examined. An update on ACTH resistance and adrenal Cushing's syndrome is provided. Finally, the role of adrenal steroidogenesis in arterial hypertension and fetal programming of adrenal androgen excess as a possible explanation for polycystic ovary syndrome in later life are analyzed. This book will be of great interest to pediatric, adult and reproductive endocrinologists, clinical geneticists, developmental biologists and basic scientists working in the fields of endocrinology and steroidogenesis.

Adrenal disease in children poses an immensely difficult diagnostic and management problem for the paediatrician in view of the large number of rare pathologies that may present in this way. This volume brings together the expertise of the acknowledged leaders in specific adrenal disorders to provide a readily accessible text that combines a detailed description of the molecular origins of these diseases, as they are currently understood, with a unique account of the clinical features and therapeutic options. Beginning with disorders that primarily affect adrenal development and progressing towards the defects that interfere with steroid production, the reader gains considerable insight into the normal physiology of the adrenal cortex particularly as revealed by clinical disorders. The major contributions of modern biochemistry and molecular genetics in our current understanding are visible throughout, providing a unique overview of adrenocortical biology. This book is of great interest to general pediatricians, paediatric endocrinologists, adult endocrinologists, clinical geneticists and basic scientists working in areas such as developmental biology and molecular steroidogenesis.

One of a series of books which aim to provide overviews of the current state of the art by specialists actively working in the field. The editors aim to focus on the borderline of our knowledge by presenting innovative results and controversial ideas.