Androgen receptor dysfunction in human androgen insensitivity.

The androgen insensitivity syndromes comprise a spectrum of phenotypic abnormalities in male sex differentiation and development that result from target tissue resistance to androgen action due to molecular lesions in the X-chromosome-linked androgen receptor gene. The androgen receptor, like other members of the superfamily of steroid receptors, is characterized by the presence of three structural domains that function in transcriptional activation, DNA binding, and steroid binding, respectively. Missense mutations in the androgen receptor gene causing amino acid substitutions are the most common molecular lesions among affected subjects; deletions, mRNA splice site alterations, and nonsense mutations occur less frequently. Because of the large number and diverse array of these naturally occurring mutations and their associated clinical phenotypes, there is a great opportunity for understanding the structure-function relationships of the androgen receptor from in vitro and in vivo expression of the mutant receptors in various cell types.