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Corticotropin Releasing Hormone And The Immune/Inflammatory Response.


Endotext [Internet]. South Dartmouth (MA):, Inc.; 2000-.
2015 Jul 30.

Author information

Professor of Medicine, University of California, San Francisco, CA
Chief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of Washington
Pediatric Endocrinologist and Associate Research Physician in the Skeletal Diseases and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health
Professor of Pediatrics and Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece
Associate Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State University
Professor of Endocrinology and Director of the Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK
Distinguished Professor of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA; Associate Chief, Endocrinology and Diabetes Division and Director, Endocrine Clinic, West Los Angeles VA Medical Center, Los Angeles, CA
Professor of General Medicine-Endocrinology, First Department of Propaedeutic Internal Medicine, Laiko University Hospital, Athens, Greece
Head of the Medicover MVZ Oldenburg; affiliated with the Carl von Ossietzky University and the Technical University of Dresden
Professor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland
Professor of Endocrinology and Metabolism, Centre Lead for Endocrinology and Deputy Institute Director, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, England
Director of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, Australia
Dammert Professor of Gerontology and Director, Division of Geriatric Medicine and Director of the Division of Endocrinology, Saint Louis University Medical Center
Professor of Pediatrics, Professor of Genetics and Genomic Sciences, and Chief of the Adrenal Steroid Disorders Program, Icahn School of Medicine, Mount Sinai School of Medicine, New York, NY
Associate Professor of Medicine and Epidemiology, University of Colorado Anschutz Medical Campus
Professor of Medicine, Knight Cardiovascular Institute and the Division of Endocrinology, and Associate Director, Bob and Charlee Moore Institute for Nutrition and Wellness, Oregon Health and Science University, Portland, OR
Professor and Chair, Department of Obstetrics and Gynecology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI
Director of the Endocrine/Bone Disease Program, John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA; Clinical Professor of Medicine, UCLA School of Medicine, Los Angeles, CA
Director of the Diabetes Care Center and Associate Professor of Medicine, University of Washington Medical Center, Seattle, WA
Murray Waitzer Endowed Chair for Diabetes Research, Professor of Medicine/Pathology/Neurobiology, Director of Research and Neuroendocrine Unit Division of Endocrine and Metabolic Disorders, Eastern Virginia Medical School, Norfolk, VA
Endowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX
Endocrine Unit, Aretaieion Hospital, Athens University, School of medicine, Vas. Sophias Av. 76 11528 Athens Greece
Endocrine Unit, 2nd Department of Obstetrics and Gynecology, Aretaieion University Hospital, Athens Medical School, Athens, Greece
Endocrine Unit, ARETAIEION Hospital, Athens University School of Medicine, 76 V. Sophias Ave, 11528, Athens


The immune/inflammatory (I/I) response is a reaction of the vascularized connective tissue, characterized by the accumulation of fluid and leukocytes in extravascular tissues. In this process cellular (leukocytes and lymphocytes T, B, NK) and extra-cellular elements participate in a complex co-operative network. The balance between Th1 and Th2 is important for the immune system homeostasis. Glucocorticoids and catecholamines have a significant effect on this balance. The (I/I) response is influenced by the brain via regulation of peripheral nervous system functions and endocrine responses. The hypothalamic-pituitary-adrenal (HPA) axis is particularly involved in this regulation. Hypothalamic corticotropin-releasing hormone (CRH) is pivotal in the HPA axis response to stress while it acts indirectly in an anti-inflammatory fashion because it leads to cortisol production, an anti-inflammatory hormone. CRH in plasma is bound to a high-affinity binding protein (CRH-BP) which limits its distribution and activity. The biological effects of CRH are mediated by CRH-Receptor (R)1 and CRH-R2. Receptors for a number of hormones, neurotransmitters and neuropeptides are carried by cells of the immune system. In their turn, immune cells produce CRH and corticotropin (ACTH) which act locally as autacoids during both the early and late stages of the I/I process. This locally produced CRH, so-called ‘peripheral CRH’, is found in the adrenal medulla, the testes, the ovaries, the cardiovascular system, the gastrointestinal tract, the pancreas, the lung, the spinal cord, the endometrium and the placenta, as well as in diverse inflammatory sites. In the latter it acts in a pro-inflammatory fashion while most of the CRH effects in the female reproductive tract seem to be pro-inflammatory as well. This is the case in ovulation, luteolysis and blastocyst implantation. Ovarian CRH is found in the theca and stroma and in the cytoplasm of the oocyte. CRH suppresses ovarian steroidogenesis in vitro. Endometrial CRH participates in the early maternal tolerance of the semiallograft embryo. Placental CRH is synthesized in syncytiotrophoblast cells, in placental decidua and fetal membranes and is secreted into the maternal circulation during gestation. Its concentrations increase as pregnancy progresses and it participates in the physiology of pregnancy and the onset of parturition. The placental CRH/CRH-R system has been associated with the pathological mechanisms leading to preeclampsia. The expression of CRH and CRH-Rs in several components of the immune system and their participation in the regulation of inflammatory phenomena led researchers to suggest CRH antagonists/inhibitors as potential therapeutic agents of such conditions. Αntalarmin, has been proposed as a therapeutic tool for both CNS and inflammatory disorders associated with central and peripheral CRH hypersecretion. Astressin B, a nonspecific CRH receptor antagonist, accelerates the return to normal cyclicity. Thus, it emerges as a potential therapeutic agent in stress-related endocrine dysfunction, including the functional hypothalamic chronic anovulation syndrome or the persistent inadequate luteal phase syndrome, and therefore in the treatment of infertility. CRH-R1 antagonists could be considered for the treatment of allergic conditions (asthma, eczema, urticaria) and in the treatment of lower gastro-intestinal inflammatory diseases associated to CRH (chronic inflammatory bowel syndromes, irritable bowel disease and ulcerative colitis). For complete coverage of this and related topics, please visit

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