AUTHOR=Ghaddhab Chiraz , Vuissoz Jean-Marc , Deladoëy Johnny 

TITLE=From Bioinactive ACTH to ACTH Antagonist: The Clinical Perspective

JOURNAL=Frontiers in Endocrinology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2017.00017

DOI=10.3389/fendo.2017.00017

ISSN=1664-2392

ABSTRACT=<p>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 <xref ref-type="fig" rid="F1">1</xref>A). 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 H<sub>6</sub>F<sub>7</sub>R<sub>8</sub>W<sub>9</sub> and K<sub>15</sub>K<sub>16</sub>R<sub>17</sub>R<sub>18</sub>P<sub>19</sub>. Most POMC-derived polypeptides contain the H<sub>6</sub>F<sub>7</sub>R<sub>8</sub>W<sub>9</sub> sequence 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.</p>