THE ROLE OF DAX-1 IN REPRODUCTION

Mutations in a gene referred to as Dax-1 cause an X-linked form of adr enal hypoplasia congenita (AHC). The disorder is limited to males and is characterized by neonatal adrenal insufficiency and failure to unde rgo puberty because of hypogonadotropic hypogonadism. Consistent with these clinical manifestations, the Dax-1 gene is expressed in the adre nal gland, gonads, hypothalamus and pituitary gland The DAX-1 protein is structurally related to orphan nuclear receptors, although it lacks the characteristic zinc finger DNA-binding domain that is highly cons erved in other members oft his family. Dax-1 has been shown to repress the transcription of genes that ave regulated by another nuclear rece ptor, steroidogenic factor-1 (SF-1). AHC mutations in Dax-1 eliminate its repressive activity. Genetic testing for Dax-1 mutations will enha nce our ability to diagnose and treat AHC. Studies of the biological v ole of Dax-1 will provide new insights into the development and functi on of the adrenal gland and the reproductive axis.