title: Adrenal gland development and defects.
abstract: The network regulating human adrenal development is complex. Studies of patients with adrenal insufficiency due to gene mutations established a central role for transcription factors GLI3, SF1 and DAX1 in the initial steps of adrenal formation. Adrenal differentiation seems to depend on adrenocorticotropic hormone (ACTH) stimulation and signalling, including biosynthesis and action of POMC, PC1, TPIT, MC2R, MRAP and ALADIN, all of which cause adrenocortical hypoplasia when mutated in humans. Studies of knockout mice revealed many more factors involved in adrenal development; however, in contrast to rodents, in humans several of those factors had no adrenal phenotype when mutated (e.g. WT1, WNT4) or, alternatively, human mutations have not (yet) been identified. Tissue profiling of fetal and adult adrenals suggested 69 genes involved in adrenal development. Among them were genes coding for steroidogenic enzymes, transcription and growth factors, signalling molecules, regulators of cell cycle and angiogenesis, and extracellular matrix proteins; however, the exact role of most of them remains to be elucidated.
authors.affiliation: Pediatric Endocrinology and Diabetology, University Children's Hospital, University of Berne, Freiburgstrasse 15, 3010 Bern, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Kempná
authors.forename: Christa E
authors.initials: CE
authors.lastname: Flück
mesh_terms: D000302:Adrenal Cortex / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development; D000307:Adrenal Gland Diseases / Q000235:genetics / Q000503:physiopathology; D000311:Adrenal Glands / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development*; D000328:Adult; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D018345:Mice, Knockout