Abstract

Androgen insensitivity syndromes represent one cause of human male pseudohermaphroditism related to defects in the androgen receptor. The formation of a biologically active androgen receptor complex with testosterone and 5 alpha-dihydrotestosterone is required for normal androgen action during fetal development and differentiation of the internal accessory sex glands and external genitalia. Cloning of the human androgen receptor complementary DNA and genetic screening of human subjects with the clinical and biochemical features of androgen insensitivity using the polymerase chain reaction, denaturing gradient gel electrophoresis and nucleotide sequencing techniques have led to the identification of molecular defects in the androgen receptor. The complexity of phenotypic presentation by affected subjects with the complete or partial forms of androgen insensitivity is represented by the heterogeneity of androgen receptor gene mutations which include deletions and point mutations, with the latter causing inappropriate splicing of RNA, premature termination of transcription and amino acid substitutions. The naturally occurring mutations in the androgen receptor of subjects with androgen insensitivity represent a base upon which we can increase our understanding of the structure and function of the androgen receptor in normal physiology and disease.