A. Petroni

G. Uziel

M. Armiraglio

M. Blasevich

M. Cappa

English

AIR Universita degli studi di Milano

Effect of steroid hormones on lipid metabolism and ABCD transporters in the neurodegenerative disease X-linked AdrenoleukodystrophyM.Armiraglio 1, M.Blasevich1, G.Uziel2 , M. Cappa3 and A.Petroni1,1Department of Pharmacological Sciences, University of Milan , via Balzaretti 9, 20133, Milan, Italy; 2 Child Neurology Department, Istituto Nazionale Neurologico “C. Besta”, Milan; 3Department of Pediatrics Medicine, Endocrinology Unit, Children’s Hospital “Bambino Gesù”, IRCCS, Rome, Italy.X-linked Adrenoleukodystrophy (X-ALD) is an inherited disorder severely affecting the nervous system. Due to the mutation of the ABCD1 gene, which encodes the peroxisomal ABCD transporter ALDP, peroxisomal beta-oxidation is impaired and  Very Long Chain Fatty Acids (VLCFA) abnormally accumulate in all tissues, although only the nervous system,   the adrenal cortex and the testis are mainly affected.  Due to the  specific  impairment of these districts we have hypothesized an involvement of steroid hormones in the pathogenesis of the disease.We have demonstrated that the androgen dihydrotestosterone (DHT) and 5-androstan-3,17-diol (3-diol) had an effect in reducing the abnormal accumulation of VLCFA, in fibroblasts from X-ALD patients and controls.      In order to further investigate these mechanisms we aimed to evaluate the effect of the androgens on the peroxisomal ABCD-transporters. ALDP is supposed to form a dimer with itself or with one of other peroxisomal ALDP-related proteins encoded by ABCD2, ABCD3 and ABCD4 genes.  We have investigated if androgens could induce ALDP-related proteins in order to compensate for the missing or impaired ALDP function induced by the mutation.  Androgens, incubated at the concentration 10-6 M in X-ALD fibroblasts, significantly enhanced peroxisomal beta-oxidation and modified mRNA levels  of ALDP-related proteins, evaluated by Real Time PCR.  The possible role of androgens in the pathogenesis of X-ALD is under investigation.

Effect of steroid hormones on lipid metabolism and ABCd trasporters in the neurodegenerative disease x-linked adrenoleukodystrophy

https://air.unimi.it/bitstream/2434/153369/2/abstract%20Milano%2005.doc

Effect of steroid hormones on lipid metabolism and ABCd trasporters in the neurodegenerative disease x-linked adrenoleukodystrophy

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AIR Universita degli studi di Milano