Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy |
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Authors: | I Roglio R Bianchi S Giatti G Cavaletti D Caruso S Scurati D Crippa L M Garcia-Segura F Camozzi G Lauria R C Melcangi |
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Institution: | (1) Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133 Milano, Italy;(2) Department of Molecular Biochemistry and Pharmacology, ”Mario Negri” Institute for Pharmacological Research, Milano, Italy;(3) Department of Neurosciences and Biomedical Technologies, University of Milan ”Bicocca”, Monza, Italy;(4) Department of Pharmacological Sciences, University of Milan, Milano, Italy;(5) Schering SpA, Segrate (Milano), Italy;(6) Instituto Cajal, C.S.I.C, Madrid, Spain;(7) Neuromuscular Diseases Unit, National Neurological Institute “Carlo Besta”, Milano, Italy |
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Abstract: | In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5αandrostan-3α, 17β-diol (3α-diol)
therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted
in decreased T and increased 3α-diol levels in plasma and in decreased levels of pregnenolone and DHT in the sciatic nerve.
Moreover, a reduced expression of the enzyme converting Tinto DHT (i.e., the 5α-reductase) also occurs at the level of sciatic nerve, suggesting that the decrease of DHT levels could be due to
an impairment of this enzyme. Chronic treatment for 1 month with DHT or 3α-diol increased tail nerve conduction velocity and
partially counteracted the increase of thermal threshold induced by diabetes. Treatment with DHT increased tibial Na+,K+-ATPase activity and the expression of myelin protein P0 in the sciatic nerve.DHT, 3α-diol and T reversed the reduction of
intra-epidermal nerve fiber density induced by diabetes. These observations indicate that T metabolites can reverse behavioral,
neurophysiological, morphological and biochemical alterations induced by peripheral diabetic neuropathy.
I. Roglio, R. Bianchi: These authors contributed equally to this study.
Received 4 January 2007; received after revision 13 February 2007; accepted 27 March 2007 |
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Keywords: | Neuroactive steroids rat sciatic nerve streptozotocin dihydrotestosterone 3α -diol 5α -reductase androgen receptor |
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