Synthesis and actions of 5α-reduced metabolites of testosterone in the nervous system

Neuroactive testosterone metabolites synthesized by enzymes 5a-reductase and 3a/3b-hydroxysteroid oxidore-ductase are critical physiological modulators of the central nervous system (CNS) function. Indeed, as discussedin this review, they exert a variety of effects on myelination, brain maturation, neurotransmission, reproductivebehavior, and the stress responses. The expression and synthesis of these enzymes as well as the levels of tes-tosterone derivatives exhibit specific localized regional and sex differences in the CNS and are influenced undervarious physiological and neuropathological conditions. In addition, neuroactive metabolites of testosteroneexert a variety of neuroprotective effects in several neuropathological animal models. Therefore, neuroactive tes-tosterone metabolites might represent an interesting potential therapeutic option to treat some neurological disorders.