Physiopathological Role of the Enzymatic Complex 5α-Reductase and 3α/β-Hydroxysteroid Oxidoreductase in the Generation of Progesterone and Testosterone Neuroactive Metabolites

The document from April 1, 2020, examines the role of the enzymes 5α-reductase (5a-R) and 3α/β-hydroxysteroid oxidoreductase (HSOR) in converting progesterone (PROG) and testosterone (T) into neuroactive metabolites within the nervous system. These metabolites are implicated in a range of neural functions and their levels vary by region, sex, and physiological conditions, and are altered in neurodegenerative and psychiatric disorders. The document discusses the potential therapeutic applications of synthetic analogues of these steroids or modulation of 5a-R for treating nervous system pathologies, but also notes the need for further research to understand the consequences of such treatments. It also highlights the neuroprotective effects of PROG and T metabolites, the development of synthetic analogues to overcome limitations of natural metabolites, and the potential adverse effects of inhibiting 5α-reductase. The document concludes that while there is evidence supporting the therapeutic use of these metabolites and their analogues, more research is necessary to confirm their efficacy and safety in humans, taking into account long-term effects and sex-specific responses.