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.