Physiopathological role of the enzymatic complex 5 alpha-reductase and 3 alpha/beta-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites

The enzymatic complex 5 alpha-reductase (5 alpha-R) and 3 alpha/3 beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone (PROG) and testosterone (T) into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5 alpha-R and 3 alpha-HSOR and the levels of PROG and T reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. However, in other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5 alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. However, further research is needed to fully understand the consequences of these manipulations, in particular with 5 alpha-R inhibitors.