Corticotropin Releasing Hormone And The Immune/Inflammatory Response

Markella Nezi; George Mastorakos; Zadalla Mouslech

Corticotropin Releasing Hormone And The Immune/Inflammatory Response

Review

In: Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000.

2015 Jul 30.

Authors

Markella Nezi¹, George Mastorakos², Zadalla Mouslech³

Book Editors

Kenneth R Feingold¹, Bradley Anawalt², Marc R Blackman³, Alison Boyce⁴, George Chrousos⁵, Emiliano Corpas⁶, Wouter W de Herder⁷, Ketan Dhatariya⁸, Kathleen Dungan⁹, Johannes Hofland¹⁰, Sanjay Kalra¹¹, Gregory Kaltsas¹², Nitin Kapoor¹³, Christian Koch¹⁴, Peter Kopp¹⁵, Márta Korbonits¹⁶, Christopher S Kovacs¹⁷, Wendy Kuohung¹⁸, Blandine Laferrère¹⁹, Miles Levy²⁰, Elizabeth A McGee²¹, Robert McLachlan²², Maria New²³, Jonathan Purnell²⁴, Rakesh Sahay²⁵, Amy S Shah²⁶, Frederick Singer²⁷, Mark A Sperling²⁸, Constantine A Stratakis²⁹, Dace L Trence³⁰, Don P Wilson³¹

Affiliations

¹ Endocrine Unit, Aretaieion Hospital, Athens University, School of medicine, Vas. Sophias Av. 76 11528 Athens Greece
² Endocrine Unit, 2nd Department of Obstetrics and Gynecology, Aretaieion University Hospital, Athens Medical School, Athens, Greece
³ Endocrine Unit, ARETAIEION Hospital, Athens University School of Medicine, 76 V. Sophias Ave, 11528, Athens

Book Affiliations

¹ Professor of Medicine Emeritus, University of California, San Francisco, CA
² Chief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of Washington
³ Sr. Physician Scientist, Washington DC VA Medical Center; Professor of Medicine & Rehabilitation Medicine, Georgetown University; Clinical Professor of Medicine, Biochemistry and Molecular Medicine, George Washington University; and Professor of Medicine (Part-time), Johns Hopkins University
⁴ 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
⁵ 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
⁶ M.D. Ph.D in Gerontology. Honorary Professor of Medicine, Universidad de Alcalá, Madrid. Consultant in Endocrinology, Hospital HLA Guadalajara (Spain).
⁷ Professor of Endocrine Oncology, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
⁸ Consultant in Diabetes, Endocrinology and General Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK.
⁹ Professor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State University
¹⁰ Consultant Endocrinologist, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
¹¹ Consultant Endocrinologist, Department of Endocrinology, Bharti Hospital, Karnal, India
¹² Professor of General Medicine-Endocrinology, 1st Department of Propaedeutic Medicine, National and Kapodistrian University of Athens, Athens, Greece
¹³ Professor of Endocrinology, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Australia.
¹⁴ Professor, The University of Tennessee Health Science Center, Memphis, Tennessee
¹⁵ Professor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland
¹⁶ 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
¹⁷ University Research Professor and Professor of Medicine (Endocrinology and Metabolism), Obstetrics & Gynecology, and BioMedical Sciences, at Memorial University of Newfoundland in St. John’s, Newfoundland, Canada.
¹⁸ Director of the Division of Reproductive Endocrinology at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at the Boston University School of Medicine
¹⁹ Professor of Medicine, New York Nutrition Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
²⁰ Consultant endocrinologist at University Hospitals of Leicester and Honorary Associate Professor at Leicester University
²¹ Professor of Obstetrics and Gynecology at the University of Vermont and Director of the Division of Reproductive Endocrinology and Infertility. Burlington, Vermont
²² Director of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, Australia
²³ 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
²⁴ 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
²⁵ Professor and Head of Department of Endocrinology, Osmania Medical College and Osmania General Hospital, Hyderabad, India.
²⁶ Professor of Pediatrics, The University of Cincinnati, Department of Pediatrics and Cincinnati Children’s Hospital Medical Center, Division of Endocrinology, Cincinnati, OH, USA
²⁷ Director of the Endocrine/Bone Disease Program, Saint Johns Cancer Institute at Saint John’s Health Center, Santa Monica, CA; Clinical Professor of Medicine, UCLA School of Medicine, Los Angeles, CA
²⁸ Professorial Lecturer, Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, New York, NY. Emeritus Professor and Chair, Department of Pediatrics, University of Pittsburgh.
²⁹ CSO, ELPEN, Inc. & Director, Research Institute, Athens, Greece & Senior Investigator, Human Genetics & Precision Medicine, FORTH (ITE), Heraklion, Greece. Emeritus Scientific Director & Senior Investigator, NICHD, NIH, Bethesda, MD, USA
³⁰ Professor of Medicine, Emeritus, University of Washington, Seattle, WA
³¹ Endowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX

PMID: 25905246
Bookshelf ID: NBK279017

Excerpt

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 www.endotext.org.

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