title: From Bioinactive ACTH to ACTH Antagonist: The Clinical Perspective.
abstract: The adrenocorticotropic hormone (ACTH) is a pituitary hormone derived from a larger peptide, the proopiomelanocortin (POMC), as are the MSHs (α-MSH, β-MSH, and γ-MSH) and the β-LPH-related polypeptides (Figure 1A). ACTH drives adrenal steroidogenesis and growth of the adrenal gland. ACTH is a 39 amino acid polypeptide that binds and activates its cognate receptor [melanocortin receptor 2 (MC2R)] through the two regions H6F7R8W9and K15K16R17R18P19. Most POMC-derived polypeptides contain the H6F7R8W9sequence that is conserved through evolution. This explains the difficulties in developing selective agonists or antagonists to the MCRs. In this review, we will discuss the clinical aspects of the role of ACTH in physiology and disease, and potential clinical use of selective ACTH antagonists.
authors.affiliation: Endocrinology Service and Research Center, Sainte-Justine University Hospital Center, Department of Pediatrics, Université de Montréal , Montreal, QC , Canada.
authors.forename: Chiraz
authors.initials: C
authors.lastname: Ghaddhab
authors.affiliation: Division of Pediatric Endocrinology, University Children's Hospital Basel (UKBB), University of Basel , Basel , Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Vuissoz
authors.affiliation: Endocrinology Service and Research Center, Sainte-Justine University Hospital Center, Department of Pediatrics, Université de Montréal , Montreal, QC , Canada.
authors.forename: Johnny
authors.initials: J
authors.lastname: Deladoëy
keywords: ACTH; adrenals; antagonist; cortisol; stress