Neurosteroids: a novel function of the brain

Neurosteroids are synthetized in the central and peripheral nervous system, particularly but not exclusively in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources. They include 3-hydroxy-delta 5-compounds, such as pregnenolone (PREG) and dehydroepiandrosterone (DHEA), their sulfates, and reduced metabolites such as the tetrahydroderivative of progesterone 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha, 5 alpha-TH PROG). These compounds can act as allosteric modulators of neurotransmitter receptors, such as GABAA, NMDA and sigma receptors. Progesterone (PROG) is also a neurosteroid, and a progesterone receptor (PROG-R) has been identified in peripheral and central glial cells. At different places in the brain, neurosteroid concentrations vary according to environmental and behavioral circumstances, such as stress, sex recognition and aggressiveness. A physiological function of neurosteroids in the central nervous system is strongly suggested by the role of hippocampal PREGS with respect to memory, observed in aging rats. In the peripheral nervous system, a role for PROG synthesized in Schwann cells has been demonstrated in the repair of myelin after cryolesion of the sciatic nerve in vivo and in cultures of dorsal root ganglia neurites. It may be important to study the effect of abnormal neurosteroid concentrations/metabolism with a view to the possible treatment of functional and trophic disturbances of the nervous system.