Role of Orphan Nuclear Receptor DAX-1/NR0B1 in Development, Physiology, and Disease

Abstract

is an unusual orphan receptor that has a pivotal role in the development and function of steroidogenic tissues and of the reproductive axis. Recent studies have also indicated that this transcription factor has an important function in stem cell biology and in several types of cancer. Here I critically review the most important findings on the role of DAX-1 in development, physiology, and disease of endocrine tissues since the cloning of its gene twenty years ago.

Gene dosage of DAX-1, determining in sexual differentiation: duplication of DAX-1 in two sisters with gonadal dysgenesis

“…Moreover, SOX9 activates SF-1 and both SOX9 and SF-1 activate anti-Müllerian hormone gene, AMH [4,34]. Interestingly, it has also been reported that DAX-1 inhibits SF-1 [34], and may have an antagonistic effect over SOX9 by inhibiting SF-1 activation of SOX9 [4,34]. The expression profile of the genes evaluated of both sisters seem to be collaborating in a 46,XY male-to-female reversal as seen in Fig.…”

“…Additionally, qPCR also showed evidence of decreased SF-1 and SOX9 expression in both sisters in reference to control tissue, antagonistically to the typical process of male differentiation in which SOX9 is known to play a pivotal role in testis development, and chondriogenic tissue and thus inhibition of this gene further blocks testis development. Moreover, SOX9 activates SF-1 and both SOX9 and SF-1 activate anti-Müllerian hormone gene, AMH [4,34]. Interestingly, it has also been reported that DAX-1 inhibits SF-1 [34], and may have an antagonistic effect over SOX9 by inhibiting SF-1 activation of SOX9 [4,34].…”

Pediatric Adrenocortical Tumors: What They Can Tell Us on Adrenal Development and Comparison with Adult Adrenal Tumors

“…Defects in this process may cause the cytomegalic form of adrenal hypoplasia congenita, a syndrome of adrenal insufficiency due to altered postnatal adrenocortical differentiation due to mutations in the NR0B1 ( DAX-1 ) gene [reviewed in Ref. ( 6 )]. Studies in pre-term neonates have shown that parturition itself is the cause for fetal adrenal involution ( 7 ), suggesting a crosstalk between placenta and fetal adrenal in reciprocal maintenance.…”

TNF-α-mediated suppression of Leydig cell steroidogenesis involves DAX-1

“…DAX-1 is mainly expressed in steroidogenic tissues including adrenal cortex, ovary and Leydig cells [10]. The DAX-1 deficient mice have testicular and spermatogenic defects with loss of germ cells and degeneration of the seminiferous epithelium [11].…”