ABNORMAL ANDROGEN RECEPTOR-BINDING AFFINITY IN SUBJECTS WITH KENNEDYSDISEASE (SPINAL AND BULBAR MUSCULAR-ATROPHY)

We have investigated androgen-binding properties of the androgen recep tor (AR) in cultured suprapubic skin fibroblasts from six subjects wit h Kennedy's disease (X-linked spinal and bulbar muscular atrophy). Bin ding of the synthetic androgen methyltrienolone (R1881) was measured i n a monolayer assay, and Scatchard analysis was performed to determine the total number of binding sites and the apparent binding affinity ( K-d) Of the AR for androgen. Five of the six subjects investigated had an abnormal apparent binding affinity, with K-d values ranging from 0 .34 - 11.7 nmol/L, more than 2 so from the mean of the normal range (0 .19 +/- 0.06 nmol/L). In this group of six patients, there was a signi ficant correlation between the AR K-d and the severity of testicular a trophy and gynecomastia. The number of CAG repeats in the expanded reg ion of exon A of the AR gene was determined in all subjects from whom suprapubic skin fibroblasts were cultured and an additional 12 subject s with Kennedy's disease. In the total group of 18 subjects investigat ed, there was a trend for an increasing number of CAG repeats associat ed with decreasing age at onset of different symptoms; however, this c orrelation was not statistically significant. Thus, we report for the first time a quantitative abnormality of the AR apparent binding affin ity in subjects with Kennedy's disease, which appears to be related to the severity of the symptoms of androgen insensitivity.