Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Medical School, 303 East Chicago Avenue, Tarry Building 15-709, Chicago, IL 60611, USA.
Trends Endocrinol Metab. 1998 Jul;9(5):169-75. doi: 10.1016/s1043-2760(98)00048-4.
Mutations in a gene referred to as Dax-1 cause an X-linked form of adrenal hypoplasia congenita (AHC). The disorder is limited to males and is characterized by neonatal adrenal insufficiency and failure to undergo puberty because of hypogonadotropic hypogonadism. Consistent with these clinical manifestations, the Dax-1 gene is expressed in the adrenal 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 conserved in other members of this family. Dax-1 has been shown to repress the transcription of genes that are regulated by another nuclear receptor, steroidogenic factor-1 (SF-1). AHC mutations in Dax-1 eliminate its repressive activity. Genetic testing for Dax-1 mutations will enhance our ability to diagnose and treat AHC. Studies of the biological role of Dax-1 will provide new insights into the development and function of the adrenal gland and the reproductive axis.
一个称为 Dax-1 的基因突变会导致一种 X 连锁先天性肾上腺发育不全（AHC）。这种疾病仅发生于男性，其特征是新生儿肾上腺功能不全，由于促性腺激素低下性性腺功能减退症而未能经历青春期。与这些临床表现一致，Dax-1 基因在肾上腺、性腺、下丘脑和垂体中表达。DAX-1 蛋白在结构上与孤儿核受体有关，尽管它缺乏该家族其他成员高度保守的特征性锌指 DNA 结合结构域。已经表明 Dax-1 可以抑制受另一个核受体——类固醇生成因子-1（SF-1）调节的基因的转录。Dax-1 中的 AHC 突变消除了其抑制活性。Dax-1 基因突变的遗传检测将提高我们诊断和治疗 AHC 的能力。对 Dax-1 生物学作用的研究将为肾上腺和生殖轴的发育和功能提供新的见解。
