Testosterone metabolites in patients reduce the levels of very long chain fatty acids accumulated in X-adrenoleukodystrophic fibroblasts

Testosterone metabolites (dihydrotestosterone, DHT) and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol), but not testosterone itself, were shown to reduce the levels of very long chain fatty acids which accumulate in cu ltured skin fibroblasts from X-adrenoleukodystrophic patients (X-ALD). In a ddition, in X-ALD fibroblasts, testosterone is less actively converted into DHT vs. controls (skin fibroblasts retrieved from normal subjects) whereas the additional conversion of DHT to the final product 3 alpha-diol is enha nced. This is the first report of altered testosterone metabolism in X-ALD fibroblasts and of the effects of androgens in lowering the abnormal accumu lation of very long chain fatty acids in this type of cells. (C) 2000 Elsev ier Science Ireland Ltd. All rights reserved.