Dihydroprogesterone increases the gene expression of myelin basic protein in spinal cord of diabetic rats.
Alterations in myelin membranes, as well as in the expression of myelin proteins have been reported in experimental models of diabetes. Data here reported show for the first time that the mRNA levels of two isoforms of myelin basic protein (MBP), 18.5 and 21.5 kDa, are decreased in the spinal cord of streptozotocin-treated rats and that treatment with a neuroactive steroid, such as progesterone (P), may counteract this effect. Interestingly, metabolism of progesterone into dihydroprogesterone (DHP) by the enzyme 5alpha-reductase seems to exert an important role in such an effect. As here demonstrated, 5alpha-reductase mRNA and DHP levels are reduced by diabetes in spinal cord, but treatment with P, is able to counteract these effects. Moreover, treatment with DHP is able to mimic the effect of P on MBP gene expression. Thus, the effects of P here observed are due to its enzymatic conversion into DHP. Because DHP, like P, interacts with P receptor (PR), the present results may suggest the importance to analyze the effects of PR modulators as tools of therapeutic strategies for diabetic complications occurring in nervous system.
Pesaresi
Marzia
M
Department of Endocrinology, Pathophysiology, and Applied Biology, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
Giatti
Silvia
S
Calabrese
Donato
D
Maschi
Omar
O
Caruso
Donatella
D
Melcangi
Roberto Cosimo
RC
D004092:20-alpha-Dihydroprogesterone / Q000494:pharmacology*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D004676:Myelin Basic Protein / Q000096:biosynthesis / Q000235:genetics*; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D004676:Myelin Basic Protein; D020033:Protein Isoforms; D004092:20-alpha-Dihydroprogesterone; D011374:Progesterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase