Synthesis and Actions of 5α-Reduced Metabolites of Testosterone in the Nervous System

Abstract

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