ACTH Action on the Adrenals

Anna Angelousi; Andrew N. Margioris; Christos Tsatsanis

ACTH Action on the Adrenals

Review

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

2020 Jun 13.

Authors

Anna Angelousi¹, Andrew N. Margioris², Christos Tsatsanis²

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 Department of Internal Medicine, National and Kapodistrian University of Athens
² Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Heraklion 71110, Crete, Greece

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: 25905342
Bookshelf ID: NBK279118

Excerpt

The adrenocorticotropin hormone (ACTH) is synthesized by the corticotroph cells of the anterior pituitary gland. ACTH, a post-translational product of the proopiomelanocortin protein (POMC), is a 39-amino acid peptide, its sequence being highly conserved in mammals. ACTH binds to the highly specific, for ACTH, melanocortin (MC) 2 receptors (MC2R) located on the surface of adrenal zona fasciculata cells producing cortisol. MC2R belongs to a superfamily of type 1 G protein-coupled receptors. The family of melanocortin receptors includes five members each having characteristic size, tissue distribution, and biological significance. Thus, the MC1R is the principal melanocortin receptor in the skin where it regulates its pigmentation. The MC3R and the MC4R in the central nervous system regulate food intake and energy homeostasis, and knockout animals for these receptors are obese. The MC5R exhibits a wide distribution although its levels in the central nervous system are low. In the adrenal cortex, it induces aldosterone production from the zona glomerulosa cells. ACTH-mediated cortisol synthesis from the zona fasciculata cells depends on a large number of factors of the adrenal microenvironment, such as chromaffin and immune cells, adipocytes, and adrenal innervation. Circadian rhythm of cortisol secretion is ensured by the central and peripheral local adrenal clock system. To activate ACTH the MC2R needs the presence of a small trans-membrane protein, the MC2 accessory protein (MRAP). Mutations of this protein result in the type 2 familial glucocorticoid deficiency (FGD) (FGD) syndrome. Type 1 FGD-syndrome is the result of mutations of the MC2R itself. ACTH stimulates cortisol synthesis and secretion by regulating multiple steps in the steroidogenetic pathway including an increase of the number of low-density lipoprotein (LDL) receptors and the cleavage of the side-chain of cholesterol converting it to pregnenolone, the first and rate-limiting step in cortisol production. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

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