Sex determination: A 'window' of DAX1 activity

Louisa M. Ludbrook, Vincent R. Harley

Research output: Contribution to journalReview ArticleResearchpeer-review

63 Citations (Scopus)


Traditionally, DAX1 was considered an 'anti-testis' gene because DAX1 duplications in XY individuals cause male-to-female sex reversal: dosage-sensitive sex reversal (DSS). In DSS, two active DAX1 genes on one X chromosome can abrogate testis formation. By contrast, mutations and deletions of DAX1 cause adrenal hypoplasia congenita (AHC). Although AHC patients develop testes, gonadal defects include disorganized testis cords and hypogonadotropic hypogonadism, which is not completely restored with gonadotropin or androgen therapy. Recent evidence of XY sex reversal in Dax1-deficient mice strongly supports a role for Dax1 as a 'pro-testis' gene. Therefore, perhaps DAX1/Dax1 acts within a 'window' of activity, outside of which testis formation does not occur. Here, we discuss the function and possible mechanisms of DAX1 action in male gonadogenesis.

Original languageEnglish
Pages (from-to)116-121
Number of pages6
JournalTrends in Endocrinology and Metabolism
Issue number3
Publication statusPublished - 1 Apr 2004
Externally publishedYes

Cite this