Androgens and fatty acid metabolism in X-linked Adrenoleukodystrophy

X-Adrenoleukodystrophy (X-ALD) is an inherited pathology characterized by very long-chain fatty acid accumulation in plasma as well as in different tissues. The nervous system, the adrenal cortex and the testis are primarily affected. Steroid metabolism which occurs in the adrenal cortex and in the testis might be severely impaired. We have hypothesized that steroids, in particular the androgens, might have a role in this pathology. We have demonstrated that the testosterone metabolite dihydrotestosterone (DHT) and 5alpha-androstan-3alpha,17beta-diol (3alpha-diol), but not testosterone itself, when incubated in skin fibroblasts obtained from patients affected by X-ALD, significantly reduced the abnormal accumulation of very long-chain fatty acids.