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Abstract
To determine if neurosteroids (steroids synthesized in the brain) are produced by
enzymes found in steroidogenic tissues, we determined if mRNA for five steroidogenic
enzymes could be detected in brain tissues or cultured cells. We detected mRNAs for
adrenodoxin, P450scc (cholesterol side-chain cleavage enzyme) and P450c11 beta (11
beta-hydroxylase) but not for P450c17 (17 alpha-hydroxylase/17,20 lyase) or P450c11AS
(aldosterone synthase) in rat brains and cultures of rat glial cells. P450scc mRNA
abundance in brain or primary glial cultures was approximately 0.01% of that found
in the adrenal, but more P450scc mRNA was detected in C6 glial cells. Both P450scc
and P450c11 beta mRNAs were most abundant in the cortex, but there were region-specific
differences for both mRNAs, and sex-specific differences for P450c11 beta mRNA. P450scc
mRNA was equally abundant in mixed glial cultures containing both astrocytes and oligodendrocytes
as in astrocyte-enriched cultures, and P450scc immunoreactivity co-localized with
GFAP immunoreactivity in cultured astrocytes. P450c11 beta mRNA was not detected in
the mixed primary glial cultures for the C6 glioma cell line that synthesize P450scc
mRNA, suggesting that glial cells do not synthesize P450c11 beta mRNA. Thus some of
the same enzymes involved in steroidogenesis in classic endocrine tissues are found
in a cell-specific and region-specific fashion in the brain. Neurosteroids may be
derivatives of known classic steroids, and/or may function through non-classic steroid
hormone receptors, such as GABAA, N-methyl-D-aspartate, and corticosterone receptors.