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In mice and humans, the androgen receptor ( AR ) gene, located on the X chromosome, is not known to be involved in sex determination. In the Japanese frog  Rana rugosa  the  AR  is located on the sex chromosomes (X, Y, Z and W). Phylogenetic analysis shows that the  AR  on the X chromosome ( X-AR ) of the Korean  R. rugosa  is basal and segregates into two clusters: one containing  W-AR  of Japanese  R. rugosa , the other containing  Y - AR .  AR  expression is twice as high in ZZ (male) compared to ZW (female) embryos in which the  W - AR  is barely expressed. Higher  AR -expression may be associated with male sex determination in this species. To examine whether the  Z - AR  is involved in sex determination in  R. rugosa , we produced transgenic (Tg) frogs carrying an exogenous  Z - AR . Analysis of ZW Tg frogs revealed development of masculinized gonads or ‘ovotestes’. Expression of  CYP17  and  Dmrt1 , genes known to be activated during normal male gonadal development, were up-regulated in the ZW ovotestis. Testosterone, supplied to the rearing water, completed the female-to-male sex-reversal in the  AR -Tg ZW frogs. Here we report that  Z - AR  is involved in male sex-determination in an amphibian species.

Involvement of Androgen Receptor in Sex Determination in an Amphibian Species