New findings on X-linked Adrenoleukodystrophy: 5alpha-reductase isoform 2 relative gene expression is modified in affected fibroblasts.

X-linked Adrenoleukodystrophy (X-ALD) is a neurodegenerative disease with an endocrinological component since, in addition to the nervous system, the adrenal cortex and the testis are mainly affected, with corresponding clinical signs. 5Alpha-reductase, a key enzyme in steroid hormone metabolism, catalyzes the conversion of testosterone into the potent androgen dihydrotestosterone and other metabolic steps in steroidogenesis. It is present in two isoforms, 5alpha-reductase isoform 1 and 2, that are encoded by different genes. The isoforms are differently expressed in the tissues, where they have distinct physiological relevance. Our study shows that the expression of isoform 2, evaluated by Real-Time PCR, is significantly altered in fibroblasts from patients affected by X-ALD with respect to controls, whereas isoform 1 is not affected. This is the first demonstration of an alteration of 5alpha-reductase isoform 2 gene expression in X-ALD, that may be related to the steroidogenesis impairment and to the specific organ malfunction.