DAX-1, an unusual orphan receptor at the crossroads of steroidogenic function and sexual differentiation.
The unusual orphan member of the nuclear hormone receptor superfamily DAX-1 (NR0B1) owes its name to its double role in human pathology. On one side, duplications in Xp21, containing the DAX-1 gene, cause phenotypic sex reversal in XY individuals. On the other side, DAX-1 gene mutations are responsible for adrenal hypoplasia congenita, invariably associated with hypogonadotropic hypogonadism. DAX-1 functions as a global negative regulator of steroid hormone production by repressing the expression of multiple genes involved in the steroidogenic pathway. Here we review the mechanism of DAX-1 function in adrenal and gonadal differentiation, with special emphasis on recent results showing the critical role of DAX-1 protein misfolding in the pathogenesis of adrenal hypoplasia congenita.
Lalli
Enzo
E
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, 67404 Illkirch, Strasbourg, France. ninino@igbmc.u-strasbg.fr
Sassone-Corsi
Paolo
P
D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis / Q000378:metabolism; D000311:Adrenal Glands / Q000502:physiology; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics* / Q000473:pathology; D000818:Animals; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D020125:Mutation, Missense; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000502:physiology*; D012097:Repressor Proteins / Q000737:chemistry / Q000502:physiology*; D012733:Sex Differentiation / Q000502:physiology*; D013256:Steroids / Q000378:metabolism; D014158:Transcription, Genetic
D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; C539965:NR0B1 protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D013256:Steroids