title: Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy.
abstract: In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5alphaandrostan-3alpha, 17beta-diol (3alpha-diol) therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted in decreased T and increased 3alpha-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 5alpha-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 3alpha-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, 3alpha-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.
authors.affiliation: Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133 Milano, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Roglio
authors.forename: R
authors.initials: R
authors.lastname: Bianchi
authors.forename: S
authors.initials: S
authors.lastname: Giatti
authors.forename: G
authors.initials: G
authors.lastname: Cavaletti
authors.forename: D
authors.initials: D
authors.lastname: Caruso
authors.forename: S
authors.initials: S
authors.lastname: Scurati
authors.forename: D
authors.initials: D
authors.lastname: Crippa
authors.forename: L M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: F
authors.initials: F
authors.lastname: Camozzi
authors.forename: G
authors.initials: G
authors.lastname: Lauria
authors.forename: R C
authors.initials: RC
authors.lastname: Melcangi
mesh_terms: D045930:Anabolic Agents / Q000627:therapeutic use; D015113:Androstane-3,17-diol / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000517:prevention & control*; D013196:Dihydrotestosterone / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D045930:Anabolic Agents; D018696:Neuroprotective Agents; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone