Age-dependent differences in androgen binding affinity in a family with spinal and bulbar muscular atrophy

To investigate androgen receptor (AR) function in spinal and bulbar muscular atrophy (SBMA).

A kindred was identified with five individuals carrying the AR gene CAG repeat expansion that causes SBMA. Androgen binding was measured in cultured genital skin fibroblasts from three affected individuals. One newborn, pre-symptomatic, individual showed normal androgen binding, but two older, symptomatic individuals showed a decrease in androgen binding affinity. This difference was not related to AR CAG repeat size, as all affected individuals in this kindred had 49 repeats (normal range 6-35). Post-mortem analysis in one subject confirmed the signs of androgen insufficiency in the testis, with marked seminiferous tubule atrophy, and the absence of germinal cells. The characteristic neuronal depletion in the anterior horn gray matter was also observed.

This report raises the possibility that age- or puberty-related changes in androgen binding could occur, which could potentially contribute to the progressive development of androgen resistance in affected men.