51. Physiopathological role of the enzymatic complex 5α-reductase and 3α/β-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites
- Author
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Eva Falvo, Silvia Diviccaro, Roberto Cosimo Melcangi, Silvia Giatti, Luis M. Garcia-Segura, Ministero dell'Istruzione, dell'Università e della Ricerca, Università degli Studi di Milano, Post-Finasteride Syndrome Foundation, Agencia Estatal de Investigación (España), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (España), Instituto de Salud Carlos III, and European Commission
- Subjects
Male ,0301 basic medicine ,Nervous system ,Cholestenone 5 alpha-Reductase ,medicine.medical_specialty ,3-Hydroxysteroid Dehydrogenases ,Neuroactive steroid ,Gene Expression ,Neurotransmission ,Neuroprotection ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Translocator protein of 18kd ,Oxidoreductase ,Internal medicine ,medicine ,Animals ,Humans ,Testosterone ,Progesterone ,chemistry.chemical_classification ,Sex Characteristics ,Endocrine and Autonomic Systems ,Mental Disorders ,Nervous tissue ,Finasteride ,Neuroactive steroids ,Brain ,Neurodegenerative Diseases ,Neuroprotective Agents ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Neurodegenerative disorders ,Female ,Hydroxysteroid ,Psychiatric disorders ,030217 neurology & neurosurgery - Abstract
The enzymatic complex 5α-reductase (5α-R) and 3α/3β-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 5α-R and 3α-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 5α-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 5α-R inhibitors., We acknowledge support from MIUR Progetto Eccellenza and Intramural Grant Line-B from Università degli Studi di Milano to SG and Post-Finasteride Foundation to RCM. We also acknowledge support from Agencia Estatal de Investigación, Spain (grant number BFU2017-82754-R), Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain and Fondos Feder to LM G-S.
- Published
- 2020