Androgen receptor binding studies on heterozygotes in a family with androgen insensitivity syndrome

A large family with androgen insensitivity syndrome (AIS) has been investigated, in order to detect carrier individuals and to investigate their AR binding. We have previously reported that different affected members of this family have different AR gene deletions, and, testing normal female relatives of the affected individuals, we have identified three heterozygote females all of whom carry a deletion of exon E of the AR gene. Androgen binding capacity was measured in cultured genital skin fibroblasts from normal male and female controls, the affected, and the heterozygote individuals in this family. A significant difference was found between the binding ranges for normal male foreskin and suprapubic skin fibroblasts (P < 0.005), and the three individuals with AIS had very low androgen binding capacity in their genital skin fibroblasts (2.6, 5.0, and 3.4 fmol 3HR1881/mg protein) compared to the normal range. The heterozygote females all had binding within the normal female suprapubic skin fibroblast range (12.5, 6.1, and 6.4 fmol 3HR1881/mg protein, respectively, for the three heterozygotes). Thus, we conclude that the absence of one functional AR gene in heterozygote females has not effect on AR binding capacity in cultured genital skin fibroblasts. In addition, bone mineral density was measured in the affected aunt and found to be significantly lowered at the lumbar spine (Z = -2.81) and hip (Z = -1.54); however, the role of the AR in determination of bone mineral density remains to be elucidated.