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Lalli, E. et al.

Lalli, Sassone-Corsi,

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.[1]

References

DAX-1, an unusual orphan receptor at the crossroads of steroidogenic function and sexual differentiation. Lalli, E., Sassone-Corsi, P. Mol. Endocrinol. (2003) [Pubmed]

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