ACTH Resistance: Genes and Mechanisms.

ACTH Resistance: Genes and Mechanisms. Endocr Dev. 2013;24:57-66 Authors: Meimaridou E, Hughes CR, Kowalczyk J, Chan LF, Clark AJ, Metherell LA Abstract ACTH resistance is a rare disorder typified by familial glucocorticoid deficiency (FGD), a genetically heterogeneous disease. Previously, genetic defects in FGD have been identified in the ACTH receptor gene (MC2R), its accessory protein (MRAP) and the steroidogenic acute regulatory protein gene (STAR). The defective mechanisms here are failures in ACTH ligand binding and/or receptor trafficking for MC2R and MRAP and, in the case of STAR mutations, inefficient cholesterol transport to allow steroidogenesis to proceed. Novel gene defects in FGD have recently been recognised in mini-chromosome maintenance-deficient 4 homologue (MCM4) and nicotinamide nucleotide transhydrogenase (NNT). MCM4 is one part of a DNA repair complex essential for DNA replication and genome stability, whilst NNT is involved in the glutathione redox system that protects cells against reactive oxygen species. The finding of mutations in these two genes implicates new pathogenetic mechanisms at play in FGD, and implies that the adrenal cortex is exquisitely sensitive to replicative and oxidative stresses. PMID: 23392095 [PubMed - in process]
Source: Endocrine Development - Category: Endocrinology Authors: Tags: Endocr Dev Source Type: research