Address for correspondence: PD Dr. med. Birgit Stoffel-Wagner, Institut fuer Klinische Biochemie, Universitaet Bonn, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany. Voice: +49-228-2875141; fax: +49-228-2875789 Birgit.Stoffel-Wagner{at}ukb.uni-bonn.de
Ann. N.Y. Acad. Sci. 1007: 64-78 (2003).
This paper summarizes the current knowledge concerning the biosynthesis
of neurosteroids in the human brain, the enzymes mediating these
reactions, their localization, and the putative effects of neurosteroids.
The presence of the steroidogenic enzymes cytochrome P450
SCC,
aromatase, 5
-reductase, 3
-hydroxysteroid dehydrogenase, and
17ß-hydroxysteroid dehydrogenase in the human brain
has now been firmly established by molecular biological and
biochemical studies. Their presence in the cerebral cortex and
in the subcortical white matter indicates that various cell
types, either neurons or glial cells, are involved in the biosynthesis
of neuroactive steroids in the brain. The following functions
are attributed to specific neurosteroids: modulation of GABA
A,
N-methyl-d-aspartate (NMDA), nicotinic, muscarinic, serotonin
(5-HT
3), kainate, glycine and sigma receptors, neuroprotection
and induction of neurite outgrowth, dendritic spines, and synaptogenesis.
We still do not know whether and how the steroidogenic enzymes
are involved in the pathophysiology of the nervous system. The
first clinical investigations in humans produced evidence for
an involvement of neuroactive steroids in conditions such as
fatigue during pregnancy, premenstrual syndrome, postpartum
depression, catamenial epilepsy, and depressive disorders. Further
and improved knowledge of the biochemical pathways of neurosteroidogenesis
and their actions on the brain may enable new perspectives in
the understanding of the physiology of the human brain as well
as in the pharmacological treatment of its disturbances.
