DIFFERENTIAL LOCALIZATION OF THE 5-ALPHA-REDUCTASE AND THE 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE IN NEURONAL AND GLIAL CULTURES

The activities of the 5alpha-reductase [the enzyme that converts testosterone into dihydrotestosterone (DHT)] and 3alpha-hydroxysteroid dehydrogenase [the enzyme that converts DHT into 5alpha-androstan-3alpha,17beta-diol (3alpha-diol)] have been evaluated in primary cultures of neurons, oligodendrocytes, and type 1 and 2 astrocytes obtained from fetal or neonatal rat brain. All cultures were used on the fifth day. The formation of DHT and 3alpha-diol was evaluated by incubating the different cultures with [C-14]testosterone or [C-14]DHT as substrates. The results obtained indicate that the formation of DHT takes place preferentially in neurons; however, type 2 astrocytes and oligodendrocytes also possess considerable 5alpha-reductase activity, while type 1 astrocytes show a much lower enzymatic activity. A completely different localization was observed for 3alpha-hydroxysteroid dehydrogenase. The formation of 3alpha-diol appears to be mainly, if not exclusively, present in type 1 astrocytes. 3alpha-Diol is formed in very low yields by neurons, type 2 astrocytes and oligodendrocytes. The compartmentalization of two strictly correlated enzymes (5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase) in separate central nervous system cell populations suggests the simultaneous participation of neurons and glial cells in the 5alpha-reductive metabolism of testosterone and possibly other hormonal steroids (e.g. progesterone, corticoids, etc.).