Intracellular signalling systems controlling the 5 alpha-reductase in glial cell cultures.
Glial cells are able to metabolize testosterone into DHT through the action of the enzyme 5 alpha-reductase. DHT may be further processed to 3 alpha-diol by the 3 alpha-hydroxysteroid-dehydrogenase. The aim of this study was to analyze if a modulation of two second messenger systems might be able to modify the 5 alpha-reductase and the 3 alpha-hydroxysteroid-dehydrogenase activities present in glial cells. To this purpose, the formation of DHT has been measured in rat glial cell cultures after different time of exposure to TPA, 4 alpha-Ph, an active and an inactive phorbol ester respectively, and 8-Br-cAMP. The results obtained indicate that the formation of DHT is not modified by the addition of phorbol esters. On the contrary, a statistically significant increase of 5 alpha-reductase activity, over control levels, has been observed after 6, 12, and 24 h of incubation with 8-Br-cAMP (10(-3) M). The effect of the cAMP analogue appears to be specific for the 5 alpha-reductase, since the 3 alpha-hydroxysteroid-dehydrogenase did not show any variation after exposure to the drug. In conclusion, the present data suggest that proteinkinase A (PKA) might be involved in the control of the 5 alpha-reductase in glial cells. It is postulated that nervous inputs utilizing cAMP as the second messenger might modify the activity of this enzyme in glial cells.
Melcangi
R C
RC
Department of Endocrinology, University of Milano, Italy.
Celotti
F
F
Castano
P
P
Martini
L
L
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D042944:Cholestenone 5 alpha-Reductase; D013196:Dihydrotestosterone / Q000378:metabolism; D004789:Enzyme Activation; D007425:Intracellular Membranes / Q000502:physiology*; D009457:Neuroglia / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000502:physiology*; D013739:Testosterone / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013196:Dihydrotestosterone; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013739:Testosterone; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase; D011494:Protein Kinases; D013755:Tetradecanoylphorbol Acetate