ROLE OF THE ANDROGEN RECEPTOR IN MALE SEXUAL-DIFFERENTIATION

The two androgens responsible for all aspects of male sexual different iation are testosterone and dihydrotestosterone. The action of both th ese steroids is mediated by a specific intracellular receptor, the and rogen receptor, which is a member of the nuclear receptor superfamily. The androgen receptor gene has been cloned and is located on the X ch romosome at Xq11-12. Mutations of this gene have been found in subject s with both complete and partial androgen insensitivity. In a study of 27 subjects with the androgen insensitivity syndrome, we have identif ied mutations in 14, using a rapid mutation screening assay. The same technique has also been used to determine carrier status in an affecte d family. We have also identified a mutation in two brothers who show perineal hypospadias as the only evidence of undervirilisation. Famili al severe hypospadias should therefore be included as part of the phen otypic spectrum of partial androgen insensitivity. The study of natura lly occurring mutations of the androgen receptor gene is providing fur ther information on the function of the androgen receptor and its role in normal male sexual differentiation.