Testosterone derivatives are neuroprotective agents in experimental diabetic neuropathy.
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.
Roglio
I
I
Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133 Milano, Italy.
Bianchi
R
R
Giatti
S
S
Cavaletti
G
G
Caruso
D
D
Scurati
S
S
Crippa
D
D
Garcia-Segura
L M
LM
Camozzi
F
F
Lauria
G
G
Melcangi
R C
RC
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*
D045930:Anabolic Agents; D018696:Neuroprotective Agents; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone