Differential localization of the 5 alpha-reductase and the 3 alpha-hydroxysteroid dehydrogenase in neuronal and glial cultures.
The activities of the 5 alpha-reductase [the enzyme that converts testosterone into dihydrotestosterone (DHT)] and 3 alpha-hydroxysteroid dehydrogenase [the enzyme that converts DHT into 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-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 3 alpha-diol was evaluated by incubating the different cultures with [14C]testosterone or [14C]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 5 alpha-reductase activity, while type 1 astrocytes show a much lower enzymatic activity. A completely different localization was observed for 3 alpha-hydroxysteroid dehydrogenase. The formation of 3 alpha-diol appears to be mainly, if not exclusively, present in type 1 astrocytes. 3 alpha-Diol is formed in very low yields by neurons, type 2 astrocytes and oligodendrocytes. The compartmentalization of two strictly correlated enzymes (5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase) in separate central nervous system cell populations suggests the simultaneous participation of neurons and glial cells in the 5 alpha-reductive metabolism of testosterone and possibly other hormonal steroids (e.g. progesterone, corticoids, etc.).
Melcangi
R C
RC
Department of Endocrinology, University of Milan, Italy.
Celotti
F
F
Castano
P
P
Martini
L
L
D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000378:metabolism*; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology*; D013196:Dihydrotestosterone / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009457:Neuroglia / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000201:enzymology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D015388:Organelles / Q000201:enzymology* / Q000648:ultrastructure; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism
D002250:Carbon Radioisotopes; D005904:Glial Fibrillary Acidic Protein; D013196:Dihydrotestosterone; D013739:Testosterone; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase