Human androgen insensitivity syndrome.

The clinical and pathophysiologic features of AIS provide a human model for understanding the role of androgen and its receptor in the induction and maintenance of male sex differentiation and function. Upon inspection, one is immediately impressed by the diverse nature of the mutations involved in the spectrum of AIS and the heterogeneous distribution of these mutations throughout the coding region of the AR gene. Because of the large number and diverse array of these naturally occurring mutations and their associated clinical phenotypes, there is great potential for understanding the structure-function relationships of AR from the in vitro expression of the mutant receptors in various cell lines. Future studies will be directed toward understanding the coordinate functional domains of AR, AR binding to specific androgen response elements, AR dimerization, AR phosphorylation, and AR interaction with accessory proteins that direct cell- and temporal-specific regulation of gene transactivation.