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 cultured skin fibroblasts from X-adrenoleukodystrophic patients (X-ALD). In addition, 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 enhanced. This is the first report of altered testosterone metabolism in X-ALD fibroblasts and of the effects of androgens in lowering the abnormal accumulation of very long chain fatty acids in this type of cells.
Petroni
A
A
Institute of Pharmacological Sciences, University of Milan, via Balzaretti 9, 20133, Milan, Italy. anna.petroni@unimi.it
Papini
N
N
Blasevich
M
M
Magnaghi
V
V
Cavarretta
I
I
Galli
C
C
Melcangi
R C
RC
D000326:Adrenoleukodystrophy / Q000378:metabolism* / Q000473:pathology; D002648:Child; D013196:Dihydrotestosterone / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000378:metabolism*
D005227:Fatty Acids; D013196:Dihydrotestosterone; D013739:Testosterone; C017364:hexacosanoic acid; C010210:lignoceric acid