Abstract

Individuals with androgen resistance encompass a spectrum of phenotypic abnormalities ranging from complete testicular feminization to undervirilized men. Such subjects have been classified according to the hormone-binding characteristics in genital skin fibroblasts and on the basis of the mutation in the androgen receptor (AR) gene. Antibodies to the amino-terminal region of the human AR were used to develop an immunoblot assay for the comparison of androgen binding with the amount of AR expressed in genital skin fibroblasts. In controls and 4 androgen-resistant subjects with DNA-binding domain mutations, levels of immunoreactive AR correlated closely with androgen-binding capacity. In 15 androgen-resistant subjects with qualitatively abnormal AR, immunoreactive AR levels tended to be higher than predicted from the ligand-binding capacity. Discordance between immunoreactivity and androgen binding also occurred in fibroblasts from 3 other subjects. One carries a stop codon in the AR gene and produces a truncated AR that is immunoreactive but does not bind androgen. Two carry single point mutations in the hormone-binding domain and produce immunoreactive AR that is normal in size but does not bind androgen.