title: Inherited ACTH insensitivity illuminates the mechanisms of ACTH action.
abstract: Adrenocorticotrophin (ACTH) insensitivity is a potentially lethal inherited disorder of ACTH signalling in the adrenal. Inactivating mutations of the ACTH receptor account for approximately 25% of these cases. A second genetic cause for this syndrome has recently been identified in the MRAP gene. The MRAP protein appears to function in the trafficking and cell surface expression of the ACTH receptor, and might indicate the existence of more widespread G-protein-coupled receptor trafficking mechanisms. Molecular defects underlying other causes of ACTH insensitivity syndromes will probably contribute further to our understanding of these pathways.
authors.affiliation: Department of Endocrinology, Barts and the London, Queen Mary, University of London, West Smithfield, London EC1M 6BQ, UK. a.j.clark@qmul.ac.uk
authors.forename: Adrian J L
authors.initials: AJ
authors.lastname: Clark
authors.forename: Louise A
authors.initials: LA
authors.lastname: Metherell
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cheetham
authors.forename: Angela
authors.initials: A
authors.lastname: Huebner
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001827:Body Height; D018389:Codon, Nonsense; D004351:Drug Resistance / Q000235:genetics*; D005938:Glucocorticoids / Q000172:deficiency; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D026901:Membrane Transport Proteins / Q000235:genetics; D020125:Mutation, Missense; D011401:Promoter Regions, Genetic / Q000235:genetics; D058261:Receptor Activity-Modifying Proteins; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics*; D018043:Receptors, Corticotropin / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000502:physiology
chemical_list: D018389:Codon, Nonsense; D005938:Glucocorticoids; D047908:Intracellular Signaling Peptides and Proteins; C458099:MRAP protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C495316:RTP1 protein, human; D058261:Receptor Activity-Modifying Proteins; D044103:Receptor, Melanocortin, Type 2; D018043:Receptors, Corticotropin; D043562:Receptors, G-Protein-Coupled; D000324:Adrenocorticotropic Hormone